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Cancer immunotherapy has revolutionized the treatment landscape by harnessing the power of the immune system to combat malignancies. Two of the most promising players in this field are cluster of differentiation 24 (CD24) and sialic acid‐binding Ig‐like lectin 10 (Siglec‐10), and both of them play pivotal roles in modulating immune responses. CD24, a cell surface glycoprotein, emerges as a convincing fundamental signal transducer for therapeutic intervention, given its significant implication in the processes related to tumour progression and immunogenic evasion. Additionally, the immunomodulatory functions of Siglec‐10, a prominent member within the Siglec family of immune receptors, have recently become a crucial point of interest, particularly in the context of the tumour microenvironment. Hence, the intricate interplay of both CD24 and Siglec‐10 assumes a critical role in fostering tumour growth, facilitating metastasis and also orchestrating immune evasion. Recent studies have found multiple evidences supporting the therapeutic potential of targeting CD24 in cancer treatment. Siglec‐10, on the other hand, exhibits immunosuppressive properties that contribute to immune tolerance within the tumour microenvironment. Therefore, we delve into the complex mechanisms through which Siglec‐10 modulates immune responses and facilitates immune escape in cancer. Siglec‐10 also acts as a viable target for cancer immunotherapy and presents novel avenues for the development of therapeutic interventions. Furthermore, we examine the synergy between CD24 and Siglec‐10 in shaping the immunosuppressive tumour microenvironment and discuss the implications for combination therapies. Therefore, understanding the roles of CD24 and Siglec‐10 in cancer immunotherapy opens exciting possibilities for the development of novel therapeutics. [ABSTRACT FROM AUTHOR]

Background: Cluster of differentiation 24 (CD24) is a highly glycosylated glycosylphosphatidylinositol (GPI)-anchored surface protein, expressed in various tumor cells, as a "don't eat me" signaling molecule in tumor immune. This study aimed to investigate the potential features of CD24 in pan-cancer. Methods: The correlations between 22 immune cells and CD24 expression were using TIMER analysis. R package "ESTIMATE" was used to predict the proportion of immune and stromal cells in pan-cancer. Spearman's correlation analysis was performed to evaluate the relationships between CD24 expression and immune checkpoints, chemokines, mismatch repair, tumor mutation burden and microsatellite instability, and qPCR and western blot were conducted to assess CD24 expression levels in liver hepatocellular carcinoma (LIHC). In addition, loss of function was performed for the biological evaluation of CD24 in LIHC. Results: CD24 expression was positively correlated with myeloid cells, including neutrophils and myeloid-derived suppressor cells, in various tumors, such as BLCA, HNSC-HPV, HNSC, KICH, KIRC, KIRP, TGCT, THCA, THYM, and UCEC. In contrast, anti-tumor NK cells and NKT cells showed a negative association with CD24 expression in BRCA-Her2, ESCA, HNSC-HPV, KIRC, THCA, and THYM. The top three tumors with the highest correlation between CD24 and ImmuneScore were TGCT, THCA, and SKCM. Functional enrichment analysis revealed CD24 expression was negatively associated with various immune-related pathways. Immune checkpoints and chemokines also exhibited inverse correlations with CD24 in CESC, CHOL, COAD, ESCA, READ, TGCT, and THCA. Additionally, CD24 was overexpressed in most tumors, with high CD24 expression in BRCA, LIHC, and CESC correlating with poor prognosis. The TIDE database indicated tumors with high CD24 expression, particularly melanoma, were less responsive to PD1/PD-L1 immunotherapy. Finally, CD24 knockdown resulted in impaired proliferation and cell cycle progression in LIHC. Conclusion: CD24 participates in regulation of immune infiltration, influences patient prognosis and serves as a potential tumor marker. [ABSTRACT FROM AUTHOR]

Abstract Background Cluster of differentiation 24 (CD24) is a highly glycosylated glycosylphosphatidylinositol (GPI)-anchored surface protein, expressed in various tumor cells, as a "don't eat me" signaling molecule in tumor immune. This study aimed to investigate the potential features of CD24 in pan-cancer. Methods The correlations between 22 immune cells and CD24 expression were using TIMER analysis. R package “ESTIMATE” was used to predict the proportion of immune and stromal cells in pan-cancer. Spearman's correlation analysis was performed to evaluate the relationships between CD24 expression and immune checkpoints, chemokines, mismatch repair, tumor mutation burden and microsatellite instability, and qPCR and western blot were conducted to assess CD24 expression levels in liver hepatocellular carcinoma (LIHC). In addition, loss of function was performed for the biological evaluation of CD24 in LIHC. Results CD24 expression was positively correlated with myeloid cells, including neutrophils and myeloid-derived suppressor cells, in various tumors, such as BLCA, HNSC-HPV, HNSC, KICH, KIRC, KIRP, TGCT, THCA, THYM, and UCEC. In contrast, anti-tumor NK cells and NKT cells showed a negative association with CD24 expression in BRCA-Her2, ESCA, HNSC-HPV, KIRC, THCA, and THYM. The top three tumors with the highest correlation between CD24 and ImmuneScore were TGCT, THCA, and SKCM. Functional enrichment analysis revealed CD24 expression was negatively associated with various immune-related pathways. Immune checkpoints and chemokines also exhibited inverse correlations with CD24 in CESC, CHOL, COAD, ESCA, READ, TGCT, and THCA. Additionally, CD24 was overexpressed in most tumors, with high CD24 expression in BRCA, LIHC, and CESC correlating with poor prognosis. The TIDE database indicated tumors with high CD24 expression, particularly melanoma, were less responsive to PD1/PD-L1 immunotherapy. Finally, CD24 knockdown resulted in impaired proliferation and cell cycle progression in LIHC. Conclusion CD24 participates in regulation of immune infiltration, influences patient prognosis and serves as a potential tumor marker.

Rational: Basal cells (BCs) are bronchial progenitor/stem cells that can regenerate injured airway that, in smokers, may undergo malignant transformation. As a model for early stages of lung carcinogenesis, we set out to characterize cytologically normal BC outgrowths from never-smokers and ever-smokers without cancers (controls), as well as from the normal epithelial "field" of ever-smokers with anatomically remote cancers, including lung adenocarcinoma (LUAD) and squamous cell carcinoma (LUSC) (cases). Methods: Primary BCs were cultured and expanded from endobronchial brushings taken remote from the site of clinical or visible lesions/tumors. Donor subgroups were tested for growth, morphology, and underlying molecular features by qRT-PCR, RNAseq, flow cytometry, immunofluorescence, and immunoblot. Results: (a) the BC population includes epithelial cell adhesion molecule (EpCAM) positive and negative cell subsets; (b) smoking reduced overall BC proliferation corresponding with a 2.6-fold reduction in the EpCAMpos/ITGA6 pos/CD24pos stem cell fraction; (c) LUSC donor cells demonstrated up to 2.8-fold increase in dysmorphic BCs; and (d) cells procured from LUAD patients displayed increased proliferation and S-phase cell cycle fractions. These differences corresponded with: (i) disparate NOTCH1/NOTCH2 transcript expression and altered expression of potential downstream (ii) E-cadherin (CDH1), tumor protein-63 (TP63), secretoglobin family 1a member 1 (SCGB1A1), and Hairy/enhancer-of-split related with YRPW motif 1 (HEY1); and (iii) reduced EPCAM and increased NK2 homeobox-1 (NKX2-1) mRNA expression in LUAD donor BCs. Conclusions: These and other findings demonstrate impacts of donor age, smoking, and lung cancer case-control status on BC phenotypic and molecular traits and may suggest Notch signaling pathway deregulation during early human lung cancer pathogenesis. [ABSTRACT FROM AUTHOR]

Background & Objective: CD24 is a small, highly glycosylated membrane protein whose expression is associated with tumorigenesis and theprogression of several types of cancer. Prostate adenocarcinoma is one of the most common cancers in men, and microscopic Gleason grading is an important factor affecting prognosis. This study aims to investigate the relationship between immunohistochemical expression of CD24 and its relationship with benign prostatic hyperplasia (BPH) and Gleason grade in prostate adenocarcinoma. Methods: This cross-sectional study was conducted on 163 patients, with an average age of 70.63±9.05 years, including 78 (47.9%) patients with prostate adenocarcinoma and 85 (52.1%) patients with benign prostatic hyperplasia., referred to Mostafa Khomeini Hospital in Tehran between 2018 and 2021, who underwent open prostatectomy or Trans Urethral Resection of Prostate (TURP). Immunohistochemical staining was used to evaluate CD24 expression, and Gleason grade was determined in the case of prostate adenocarcinoma. Data were analyzed with SPSS 22 and a P-value<0.05 was considered statistically significant. Results: The percentage and intensity of CD24 staining in prostate adenocarcinoma patients was significantly higher than in BPH patients (P<0.05). Gleason score strongly correlated with the percentage and intensity of CD24 staining (P<0.05). The immunoreactive score, obtained by multiplying the CD24 expression percentage with staining intensity, was also significantly related to the Gleason score (P<0.05). Conclusion: CD24 expression can be considered as a factor in differentiating cases of prostate adenocarcinoma from benign prostatic hyperplasia. Also, a high level of this marker can indicate the progress of prostate cancer. [ABSTRACT FROM AUTHOR]

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L‐type amino acid transporter 1 (LAT1) is specifically expressed in many malignancies, contributes to the transport of essential amino acids, such as leucine, and regulates the mammalian target of rapamycin (mTOR) signaling pathway. We investigated the expression profile and functional role of LAT1 in prostate cancer using JPH203, a specific inhibitor of LAT1. LAT1 was highly expressed in castration‐resistant prostate cancer (CRPC) cells, including C4‐2 and PC‐3 cells, but its expression level was low in castration‐sensitive LNCaP cells. JPH203 significantly inhibited [14C] leucine uptake in CRPC cells but had no effect in LNCaP cells. JPH203 inhibited the proliferation, migration, and invasion of CRPC cells but not of LNCaP cells. In C4‐2 cells, Cluster of differentiation (CD) 24 was identified by RNA sequencing as a novel downstream target of JPH203. CD24 was downregulated in a JPH203 concentration‐dependent manner and suppressed activation of the Wnt/β‐catenin signaling pathway. Furthermore, an in vivo study showed that JPH203 inhibited the proliferation of C4‐2 cells in a castration environment. The results of this study indicate that JPH203 may exert its antitumor effect in CRPC cells via mTOR and CD24. [ABSTRACT FROM AUTHOR]

CD24 is a glycosylphosphatidylinositol-anchored protein that is expressed in a wide range of tissues and cell types. It is involved in a variety of physiological and pathological processes, including cell adhesion, migration, differentiation, and apoptosis. Additionally, CD24 has been studied extensively in the context of cancer, where it has been found to play a role in tumor growth, invasion, and metastasis. In recent years, there has been growing interest in CD24 as a potential therapeutic target for cancer treatment. This review summarizes the current knowledge of CD24, including its structure, function, and its role in cancer. Finally, we provide insights into potential clinical application of CD24 and discuss possible approaches for the development of targeted cancer therapies. [ABSTRACT FROM AUTHOR]

Introduction: CD24 is a highly glycosylated glycosylphosphatidylinositol anchored membrane protein that plays an important role in tumor progression. The aim of this study was to investigate the effect of abnormal expression of CD24 on the proliferation, migration and invasion of breast cancer (BC) cells, and the molecular mechanism of regulating CD24 expression in breast cancer. Methodology: The bioinformatics method was used to predict the expression level of CD24 in BC and its relationship with the occurrence and development of BC. IHC, RT-qPCR and WB were used to detect the expression of CD24 in BC tissues and cells. The proliferation of CD24 was evaluated by CCK-8 and colony formation assay, and the migration and invasion of CD24 were evaluated by wound healing and transwell. In addition, the effect of CD24 on the malignancy of BC in vivo was further evaluated by subcutaneous tumorigenesis assay. Molecular mechanisms were measured by luciferase reporter assays, biotin-labeled miRNA pull-down assay, RIP, and western blotting. Results: The results show that CD24 is highly expressed in breast cancer tissues and cell lines, and knockdown of CD24 in vivo and in vitro can inhibit the proliferation, migration and invasion of BC cells. Mechanistically, the transcription factor ZNF460 promotes its expression by binding to the CD24 promoter, and the expression of ZNF460 is regulated by miR-125a-5p, which inhibits its expression by targeting the 3’UTR of ZNF460. In addition, LINC00525 acts as a ceRNA sponge to adsorb miR-125a-5p and regulate its expression. Conclusions: Overexpression of CD24 is involved in the development and poor prognosis of BC, which can be used as a potential target for the treatment of BC and provide a theoretical basis for the treatment of BC. [ABSTRACT FROM AUTHOR]

Background: Tumor immunotherapy brings new light and vitality to breast cancer patients, but low response rate and limitations of therapeutic targets become major obstacles to its clinical application. Recent studies have shown that CD24 is involved in an important process of tumor immune regulation in breast cancer and is a promising target for immunotherapy. Methods: In this study, singleR was used to annotate each cell subpopulation after t-distributed stochastic neighbor embedding (t-SNE) methods. Pseudo-time trace analysis and cell communication were analyzed by Monocle2 package and CellChat, respectively. A prognostic model based on CD24-related genes was constructed using several machine learning methods. Multiple quantitative immunofluorescence (MQIF) was used to evaluate the spatial relationship between CD24+PANCK+cells and exhausted CD8+T cells. Results: Based on the scRNA-seq analysis, 1488 CD24-related differential genes were identified, and a risk model consisting of 15 prognostic characteristic genes was constructed by combining the bulk RNA-seq data. Patients were divided into high- and low-risk groups based on the median risk score. Immune landscape analysis showed that the low-risk group showed higher infiltration of immune-promoting cells and stronger immune reactivity. The results of cell communication demonstrated a strong interaction between CD24+epithelial cells and CD8+T cells. Subsequent MQIF demonstrated a strong interaction between CD24+PANCK+ and exhausted CD8+T cells with FOXP3+ in breast cancer. Additionally, CD24+PANCK+ and CD8+FOXP3+T cells were positively associated with lower survival rates. Conclusion: This study highlights the importance of CD24+breast cancer cells in clinical prognosis and immunosuppressive microenvironment, which may provide a new direction for improving patient outcomes. [ABSTRACT FROM AUTHOR]

Abstract Background Hepatocellular carcinoma constitutes the most common primary hepatic cancer and remains a major medical burden in both developing and developed world. It ranks fifth in terms of global cases and second in terms of deaths for males.CD24 is known as a heavily glycosylated cell surface molecule that is highly expressed in a wide variety of human malignancies. It plays an important role in self-renewal, proliferation, migration, invasion, and drug resistance. The aim of this work was to evaluate the potential role of serum CD24 in the diagnosis and prediction of response to interventional therapy among hepatocellular carcinomas. Methods This study included 40 adult Egyptian patients who had liver cirrhosis and hepatocellular carcinoma (HCC group). Another group of 20 patients with liver cirrhosis only served as controls (Cirrhosis group). All patients underwent standard laboratory tests and abdominal ultrasound. For HCC patients, a triphasic CT scan, alpha-fetoprotein was done. CD24 levels were measured in all patients, and in HCC patients at baseline and one month after intervention. Results Baseline CD24 was significantly higher among HCC group in comparison to cirrhosis group (19.463 ± 8.573 vs. 0.725 ± 0.125 mg/L) with an overall p value

Abstract Introduction EXO-CD24 are exosomes genetically manipulated to over-express Cluster of Differentiation (CD) 24. It consists of two breakthrough technologies: CD24, the drug, as a novel immunomodulator that is smarter than steroids without any side effects, and exosomes as the ideal natural drug carrier. Methods A randomized, single blind, dose-finding phase IIb trial in hospitalized patients with mild to moderate Coronavirus disease 2019 (COVID-19) related Acute Respiratory Distress Syndrome (ARDS) was carried out in two medical centers in Athens. Patients received either 109 or 1010 exosome particles of EXO-CD24, daily, for five consecutive days and monitored for 28 days. Efficacy was assessed at day 7 among 91 patients who underwent randomization. The outcome was also compared in a post-hoc analysis with an income control group (n = 202) that fit the inclusion and exclusion criteria. Results The mean age was 49.4 (± 13.2) years and 74.4% were male. By day 7, 83.7% showed improved respiratory signs and 64% had better oxygen saturation (SpO2) (p

Background: Hepatocellular carcinoma constitutes the most common primary hepatic cancer and remains a major medical burden in both developing and developed world. It ranks fifth in terms of global cases and second in terms of deaths for males.CD24 is known as a heavily glycosylated cell surface molecule that is highly expressed in a wide variety of human malignancies. It plays an important role in self-renewal, proliferation, migration, invasion, and drug resistance. The aim of this work was to evaluate the potential role of serum CD24 in the diagnosis and prediction of response to interventional therapy among hepatocellular carcinomas. Methods: This study included 40 adult Egyptian patients who had liver cirrhosis and hepatocellular carcinoma (HCC group). Another group of 20 patients with liver cirrhosis only served as controls (Cirrhosis group). All patients underwent standard laboratory tests and abdominal ultrasound. For HCC patients, a triphasic CT scan, alpha-fetoprotein was done. CD24 levels were measured in all patients, and in HCC patients at baseline and one month after intervention. Results: Baseline CD24 was significantly higher among HCC group in comparison to cirrhosis group (19.463 ± 8.573 vs. 0.725 ± 0.125 mg/L) with an overall p value < 0.001. Serum CD24 levels significantly declined after locoregional treatment from 19.463 ± 8.573 mg/L to 3.569 ± 1.248 mg/L (p < 0.001). Baseline CD24 was a useful marker in eligibility for HCC intervention with 80% sensitivity and 74.29% specificity at a cutoff of ≤ 23 mg/L, and it also had 62.96% sensitivity and 100% specificity in prediction of cure after locoregional treatment at a cutoff of ≤ 19.5 mg/L. Conclusion: CD24 could be a helpful diagnostic and prognostic marker for HCC, as its baseline level is useful in predicting both eligibility for intervention and cure after locoregional treatment. [ABSTRACT FROM AUTHOR]

Background: Several long non-coding RNAs are implicated in the development and metastasis of cancer. The non-coding RNA HOTAIR is known to play a significant role in the progression of various cancers. Objectives: This study aimed to assess the impact of HOTAIR dysregulation on stemness markers in AGS and MKN45 gastric cancer cell lines. Methods: Downregulation and upregulation of HOTAIR were induced using small interfering RNA (siRNA) and a HOTAIR overexpression vector, respectively. The surface stemness markers CD24 and CD44 were analyzed using flow cytometry. Additionally, the effects on the expression of two stemness markers, NANOG and P21, were investigated using Quantitative Reverse Transcription PCR (qRT-PCR). Results: Flow cytometry analysis showed that HOTAIR modulates the cell-surface expression of CD44 and CD24 in gastric cancer cells. Furthermore, dysregulation of HOTAIR significantly affected the expression of the genes P21 and NANOG. Conclusions: Our studies suggest that HOTAIR may regulate the stemness characteristics of gastric cancer cell lines. [ABSTRACT FROM AUTHOR]

Introduction: EXO-CD24 are exosomes genetically manipulated to over-express Cluster of Differentiation (CD) 24. It consists of two breakthrough technologies: CD24, the drug, as a novel immunomodulator that is smarter than steroids without any side effects, and exosomes as the ideal natural drug carrier. Methods: A randomized, single blind, dose-finding phase IIb trial in hospitalized patients with mild to moderate Coronavirus disease 2019 (COVID-19) related Acute Respiratory Distress Syndrome (ARDS) was carried out in two medical centers in Athens. Patients received either 109 or 1010 exosome particles of EXO-CD24, daily, for five consecutive days and monitored for 28 days. Efficacy was assessed at day 7 among 91 patients who underwent randomization. The outcome was also compared in a post-hoc analysis with an income control group (n = 202) that fit the inclusion and exclusion criteria. Results: The mean age was 49.4 (± 13.2) years and 74.4% were male. By day 7, 83.7% showed improved respiratory signs and 64% had better oxygen saturation (SpO2) (p < 0.05). There were significant reductions in all inflammatory markers, most notably in C-reactive protein (CRP), lactate dehydrogenase (LDH), ferritin, fibrinogen and an array of cytokines. Conversely, levels of the anti-inflammatory cytokine Interleukin-10 (IL-10) were increased (p < 0.05). Of all the documented adverse events, none were considered treatment related. No drug-drug interactions were noted. Two patients succumbed to COVID-19. Post-hoc analysis revealed that EXO-CD24 patients exhibited greater improvements in clinical and laboratory outcomes compared to an observational income control group. Conclusions: EXO-CD24 presents a promising therapeutic approach for hyper-inflammatory state and in particular ARDS. Its unique combination of exosomes, as a drug carrier, and CD24, as an immunomodulator, coupled with inhalation administration, warrants further investigation in a larger, international, randomized, quadri-blind trial against a placebo. [ABSTRACT FROM AUTHOR]

CD24 is a protein found on the surface of cells that plays a crucial role in the proliferation, invasion, and spread of cancer cells. It adheres to cell membranes through glycosylphosphatidylinositol (GPI) and is associated with the prognosis and survival rate of cancer patients. CD24 interacts with the inhibitory receptor Siglec-10 that is present on immune cells like natural killer cells and macrophages, leading to the inhibition of natural killer cell cytotoxicity and macrophage-mediated phagocytosis. This interaction helps tumor cells escape immune detection and attack. Although the use of CD24 as a immune checkpoint receptor target for cancer immunotherapy is still in its early stages, clinical trials have shown promising results. Monoclonal antibodies targeting CD24 have been found to be well-tolerated and safe. Other preclinical studies are exploring the use of chimeric antigen receptor (CAR) T cells, antibody-drug conjugates, and gene therapy to target CD24 and enhance the immune response against tumors. In summary, this review focuses on the role of CD24 in the immune system and provides evidence for CD24 as a promising immune checkpoint for cancer immunotherapy. [ABSTRACT FROM AUTHOR]

Objectives: Our study elucidates the prognostic role of cluster of differentiation (CD) 24 expression in oral squamous cell carcinoma (OSCC) and determines whether targeting CD24 enhances the anti‐tumor immune response by inhibiting tumor‐associated macrophages (TAMs). Materials and Methods: The expression of CD24 and CD68 was analyzed immunohistochemically via tissue microarrays constructed using 56 cohorts of patients with OSCC and 20 control specimens. Further, CD24 was inhibited in an allograft squamous cell carcinoma (SCC) related mouse model with CD24mAb to determine the tumor volume and weight. Changes in immune cells such as TAMs and T cells in the tumor microenvironment (TME) were analyzed by Flow cytometry. The expression of CD4, CD8, and Ki67 was analyzed via immunohistochemistry. The inhibition of CD24 was confirmed by Western blot and immunohistochemistry. Results: CD24 was overexpressed in OSCC. High expression of CD24 indicated poor survival in patients with OSCC (p = 0.0334). CD24 expression was significantly correlated with CD68 (p = 0.0424). The inhibition of CD24 delayed tumor growth in vivo. A decrease in TAMs number and an increase in T cell number were confirmed, while the ability of tumor proliferation was impaired. Conclusion: Targeting CD24 could enhance anti‐tumor immune response by inhibiting TAMs. [ABSTRACT FROM AUTHOR]

Xudong Zhu,1,2 Jiahui Yu,3 Fulu Ai,1 Yue Wang,1 Wu Lv,1 Guilin Yu,1 Xiankui Cao,1 Jie Lin1 1Department of General Surgery, Cancer Hospital of China Medical University, Cancer Hospital of Dalian University of Technology, Liaoning Cancer Hospital and Institute, Shenyang, Liaoning, 110042, People’s Republic of China; 2Department of Oncology, Shengjing Hospital of China Medical University, Shenyang, Liaoning, 110004, People’s Republic of China; 3Department of Ultrasound, Shengjing Hospital of China Medical University, Shenyang, Liaoning, 110004, People’s Republic of ChinaCorrespondence: Jie Lin; Xudong Zhu, Department of General Surgery, Cancer Hospital of China Medical University, Cancer Hospital of Dalian University of Technology, Liaoning Cancer Hospital and Institute, Shenyang, Liaoning, 110042, People’s Republic of China, Tel +86 13940081800 ; +86 13354204706, Email linxiran0221@126.com; xdzhu@cmu.edu.cnPurpose: CD24 mediates a “don’t eat me” signal to escape the immune environment. However, the correlation between CD24 and PD-L1 is unclear. This study aimed to assess if CD24 can serve as a target for immunotherapy of triple-negative breast cancer (TNBC).Methods: Data on CD24 expression in breast cancer were acquired using the Oncomine and UALCAN tools. The role of CD24 expression on the prognosis of patients with TNBC was assessed using Kaplan–Meier analyses. Subsequently, STRING and TISIDB databases were used to construct protein–protein interaction networks and to explore immune-related molecules regulated by CD24. Immunofluorescence and immunohistochemistry assays were conducted to validate CD24 and PD-L1 expression and tumor infiltration lymphocyte (TIL) level. Survival analysis was also performed to explore the effect of CD24 and PD-L1 expression and TIL level in patients with TNBC. ShRNA was also used to explore the regulation role of CD24 on PD-L1 expression.Results: CD24 expression was significantly higher in breast cancer than in normal tissues, with high expression being significantly associated with a worse prognosis. CD24 was found to be significantly regulated by chemokines, immunoinhibitors, immunostimulators and TILs. Furthermore, CD24 expression showed a significant positive correlation with PD-L1 expression and a negative correlation with TIL level. In association with PD-L1, CD24 was found to positively regulate lymphocyte costimulation, T cell costimulation, and leukocyte activation. Furthermore, CD24 and PD-L1 co-expression contributed to worse survival outcomes. In addition, CD24 expression was found to attenuate the positive effects of high-level TILs on the prognosis of patients with TNBC. CD24 can also regulate the expression of PD-L1 in TNBC cells.Conclusion: CD24 may attenuate the positive effects of high TIL levels on survival and may facilitate the immune escape of TNBC by regulating PD-L1 expression. Thus, it is a potential target for immunotherapy in TNBC.Keywords: triple negative breast cancer, CD24, PD-L1, prognosis, immunotherapy

Background Head and neck squamous cell carcinoma (HNSCC) encompasses a diverse range of tumors with varying degrees of differentiation. Within tumors, cancer stem cells (CSCs) are believed to play a crucial role in tumor initiation, progression, and resistance to treatment. This study aimed to explore the expression of two CSC markers i.e. CD24 and Oct4, in patients with HNSCC. Methods The study included 85 patients diagnosed with HNSCC. Immunohistochemistry was used to evaluate the expression of CD24 and Oct4 in tumor tissues obtained from patients with HNSCC. Staining intensity and the proportion of positive tumor cells were analyzed and compared across the various HNSCC grades and histological subtypes. Results The findings revealed that the mean immunoreactivity score (IRS) for CD24 was significantly higher in non-conventional HNSCC subtypes compared to conventional types ( p = 0.019). Additionally, a significant statistical association was observed between the IRS status of CD24 and histological subtypes ( p = 0.043). Other demographic, clinical, and histological parameters showed non-significant associations with staining intensity, proportion score (PC), IRS status, and mean IRS (all p values > 0.05). Conclusions These findings indicate that CD24 could potentially serve as a CSC marker for distinguishing between conventional and non-conventional histological types of HNSCC. This suggests that CD24 holds promise as a valuable tool in identifying specific HNSCC subtypes characterized by CSCs.

The small, heavily glycosylated protein CD24 is primarily expressed by many immune cells and is highly expressed mostly in cancer cells. As one of the most crucial biomarkers of cancers, CD24 is frequently highly expressed in solid tumors, while tumor-associated macrophages express Siglec-10 at high levels, Siglec-10 and CD24 can interact on innate immune cells to lessen inflammatory responses to a variety of disorders. Inhibiting inflammation brought on by SHP-1 and/or SHP-2 phosphatases as well as cell phagocytosis by macrophages, the binding of CD24 to Siglec-10 can prevent toll-like receptor-mediated inflammation. Targeted immunotherapy with immune checkpoint inhibitors (ICI) has lately gained popularity as one of the best ways to treat different tumors. CD24 is a prominent innate immune checkpoint that may be a useful target for cancer immunotherapy. In recent years, numerous CD24/Siglec-10-related research studies have made tremendous progress. This study discusses the characteristics and workings of CD24/Siglec-10-targeted immunotherapy and offers a summary of current advances in CD24/Siglec-10-related immunotherapy research for cancer. We then suggested potential directions for CD24-targeted immunotherapy, basing our speculation mostly on the results of recent preclinical and clinical trials. [ABSTRACT FROM AUTHOR]

CD24 has emerged as a molecule of significant interest beyond the oncological arena. Recent studies have unveiled its surprising and diverse roles in various biological processes and diseases. This review encapsulates the expanding spectrum of CD24 functions, delving into its involvement in immune regulation, cancer immune microenvironment, and its potential as a therapeutic target in autoimmune diseases and beyond. The 'magic' of CD24, once solely attributed to cancer, now inspires a new paradigm in understanding its multifunctionality in human health and disease, offering exciting prospects for medical advancements. [ABSTRACT FROM AUTHOR]

Introduction: Disturbances of energy metabolism contribute to the clinical manifestations of myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS). Previously, we found that B cells from ME/CFS patients have an increased expression of CD24, a modulator of many cellular functions including those of cell stress. The relative ability of B cells from ME/CFS patients and healthy controls (HC) to respond to rapid changes in energy demand was compared. Methods: CD24, the ectonucleotidases CD39 and CD73, the NAD-degrading enzyme CD38, and mitochondrial mass (MM) were measured following crosslinking of the B cell receptor and costimulation with either T-cell-dependent or Toll-like-receptor-9-dependent agonists. The levels of metabolites consumed/produced were measured using 1H-NMR spectroscopy and analyzed in relation to cell growth and immunophenotype. Results: Proliferating B cells from patients with ME/CFS showed a lower mitochondrial mass and a significantly increased usage of essential amino acids compared with those from HC, with a significantly delayed loss of CD24 and an increased expression of CD38 following stimulation. Discussion: The immunophenotype results suggested the triggering of a stress response in ME/CFS B cells associated with the increased usage of additional substrates to maintain necessary ATP levels. Disturbances in energy metabolism in ME/CFS B cells were thus confirmed in a dynamic in vitro model, providing the basis for further mechanistic investigations. [ABSTRACT FROM AUTHOR]

Simple Summary: This manuscript focuses on cancer stem cells and the diagnostic potential of selected biomarkers of these cells in ovarian cancers. Ovarian cancer has nonspecific clinical symptoms. Also, there are no reliable diagnostic and prognostic biomarkers. For these reasons, nearly 70% of patients are diagnosed with ovarian cancer at the metastatic stage. The role of CSCs in ovarian cancer initiation and progression and their impact on resistance to therapy are still the subjects of many studies; however, the results are sometimes conflicting due to the heterogeneity and plasticity of CSCs. The identification of CSC phenotypes could contribute to the development of more effective diagnostic and therapeutic strategies in ovarian cancer. This is especially important since strategies to overcome resistance to conventional treatments and prolong patient survival are highly awaited. Ovarian cancer is the most lethal gynaecological cancer and the eighth most common female cancer. The early diagnosis of ovarian cancer remains a clinical problem despite the significant development of technology. Nearly 70% of patients with ovarian cancer are diagnosed with stages III–IV metastatic disease. Reliable diagnostic and prognostic biomarkers are currently lacking. Ovarian cancer recurrence and resistance to chemotherapy pose vital problems and translate into poor outcomes. Cancer stem cells appear to be responsible for tumour recurrence resulting from chemotherapeutic resistance. These cells are also crucial for tumour initiation due to the ability to self-renew, differentiate, avoid immune destruction, and promote inflammation and angiogenesis. Studies have confirmed an association between CSC occurrence and resistance to chemotherapy, subsequent metastases, and cancer relapses. Therefore, the elimination of CSCs appears important for overcoming drug resistance and improving prognoses. This review focuses on the expression of selected ovarian CSC markers, including CD133, CD44, CD24, CD117, and aldehyde dehydrogenase 1, which show potential prognostic significance. Some markers expressed on the surface of CSCs correlate with clinical features and can be used for the diagnosis and prognosis of ovarian cancer. However, due to the heterogeneity and plasticity of CSCs, the determination of specific CSC phenotypes is difficult. [ABSTRACT FROM AUTHOR]

Acute Respiratory Distress Syndrome (ARDS) is a major health concern with urgent unmet need for treatment options. There are three million new ARDS cases annually, and the disease's mortality rate is high (35–46%). Cluster of differentiation 24 (CD24), a long-known protein with multifaceted functions, is a small, heavily glycosylated, membrane-anchored protein which functions as an immune checkpoint control. CD24 allows for immune discrimination between Damage-Associated Molecular Patterns and Pathogen-Associated Molecular Patterns derived from pathogens. Exosomes are intraluminal vesicles which play an important role in intercellular communication. Exosomes offer the advantage of targeted delivery, which improves safety and efficacy. The safety and efficacy of EXO-CD24 is promising, as was shown in >180 ARDS patients in phase 1b/2a, phase 2b, and compassionate use. CD24 binds Damage-associated molecular patterns (DAMPs) and inhibits the activation of the NF-ĸB pathway, a pivotal mediator of inflammatory responses. In contrast to anti-inflammatory therapies that are cytokine-specific or steroids that shut down the entire immune system, EXO-CD24 acts upstream, reverting the immune system back to normal activity. Herein, the safety and efficacy of mEXO-CD24 is shown in murine models of several pulmonary diseases (sepsis, allergic asthma, Chronic Obstructive Pulmonary Disease(COPD), fibrosis). EXO CD24 can suppress the hyperinflammatory response in the lungs in several pulmonary diseases with a significant unmet need for treatment options. [ABSTRACT FROM AUTHOR]

Purpose: This study intends to investigate the possible molecular mechanism of immune response and tumorigenesis in ovarian cancer cells, mediated by sirtuin 1 (SIRT1)-containing extracellular vesicles (EVs) derived from cancer-associated adipocytes (CAAs) (CAA-EVs). Methods: Differentially expressed genes in EVs from CAAs were screened by RNA transcriptome sequencing, and the downstream pathway was predicted in silico. The binding between SIRT1 and CD24 was investigated by luciferase activity and ChIP-PCR assays. EVs were extracted from human ovarian cancer tissue-isolated CAAs, and the internalization of CCA-EVs by ovarian cancer cells was characterized. The ovarian cancer cell line was injected into mice to establish an animal model. Flow cytometry was performed to analyze the proportions of M1 and M2 macrophages, CD8+ T, T-reg, and CD4+ T cells. TUNEL staining was used to detect cell apoptosis in the mouse tumor tissues. ELISA detection was performed on immune-related factors in the serum of mice. Results: CAA-EVs could deliver SIRT1 to ovarian cancer cells, thereby affecting the immune response of ovarian cancer cells in vitro and promoting tumorigenesis in vivo. SIRT1 could transcriptionally activate the expression of CD24, and CD24 could up-regulate Siglec-10 expression. CAA-EVs-SIRT1 activated the CD24/Siglec-10 axis and promoted CD8+ T cell apoptosis, thereby promoting tumorigenesis in mice. Conclusion: CAA-EVs-mediated transfer of SIRT1 regulates the CD24/Siglec-10 axis to curb immune response and promote tumorigenesis of ovarian cancer cells. [ABSTRACT FROM AUTHOR]

Introduction: CD24 is often overexpressed in human tumors as a regulator of cell migration, invasion and proliferation. It has been associated with poor prognosis and chemoresistance in laryngeal cancer. In oral cavity tumors, it was correlated with better overall survival. In this study, we aimed to evaluate the role of CD24 in peripheral blood leukocytes (PBLs) as a potential marker for head and neck malignancies. Materials and Methods: CD24/CD11b expression in peripheral blood leukocytes (PBLs) of head and neck cancer patients and matched healthy controls was analyzed via flow cytometry. Tumors and healthy tissues were immune-stained for CD24 expression and the intensity of stain was ranked. Clinical data including tumor site, size, locoregional or metastatic spread, histopathological characteristics and recurrence events were analyzed. Results: CD24 expression in PBLs was significantly higher in a cohort of 101 head and neck cancer patients compared with 101 matched healthy controls (26.9 ± 12.9 vs. 22.4 ± 13.8; p = 0.02). No significant differences in CD24 levels in PBLs were found between different head and neck subsites involved with malignancy. Higher CD24 levels did not correlate with any adverse feature, i.e., perineural invasion or lymphovascular invasion, advanced T stage or regional spread. Immunohistochemistry analysis demonstrated that CD24 was highly expressed in tumor tissue in comparison to healthy surrounding tissue. Conclusions: CD24 is a possible uprising marker for tumor identification, overexpressed in PBLs and is intensely stained in tumor tissue and pre-malignant lesions. Tumor–PBLs should be further studied. [ABSTRACT FROM AUTHOR]

Background: Antibody is a considerable approach in the pharmaceutical industry, and many studies have been done on antibody fragment engineering. Objectives: The objective of this study is to evaluate the interaction between antigens and antibodies, which is a necessary step for designing an efficient antibody with suitable properties for targeting cancer cells. Methods: In the current study, the 3-dimensional structure of the displayed-selected scFv antibody was constructed, using Sabpred Antibody Builder. The analysis of interactions between scFv and Cluster of differentiation 24 (CD24) was performed by computational docking and molecular dynamics (MD) simulation. Firstly, docking CD24 antigen to the new scFv antibody was done, using the ClusPro 2.0 web server, and residues involved in the interaction were identified. Secondly, using the GROMACS 4.5.3 package, MD simulations were performed. Results: By analyzing the antigen-antibody complex, the critical amino acids involved in these interactions were recognized. Thus, 15 hydrogen bonds between amino acids in light and heavy chains of antibodies and antigens were identified; most of the amino acids belonged to the complementarity-determining regions (CDRs) regions. Tyr148, which belongs to CDR1 of the VL chain by forming 4 hydrogen bonds with amino acids of the CD24 antigen, was considered an important amino acid in the CD24-scFv complex. Conclusions: Our bioinformatics study identified critical residues involved in antigen-antibody interaction, which could be considered an effective strategy for creating novel efficient fragmented antibodies with improved affinities for the CD24 receptor. [ABSTRACT FROM AUTHOR]

Immunotherapy is a hot area in cancer treatment, and one of the keys to this therapy is the identification of the right tumour-associated or tumour-specific antigen. Cluster of differentiation 24 (CD24) is an emerging tumour-associated antigen that is commonly and highly expressed in various tumours. In addition, CD24 is associated with several cancer-related signalling pathways and closely interacts with other molecules and immune cells to influence tumour progression. Monoclonal antibodies, antibody–drug conjugates (ADCs), chimeric antigen receptor (CAR) T-cell therapy, and CAR-NK cell therapy are currently available for the treatment of CD24. In this review, we summarise the existing therapeutic approaches and possible future directions targeting CD24. [ABSTRACT FROM AUTHOR]

Abstract Cluster of differentiation 24 (CD24), a mucin-like highly glycosylated molecule has been extensively studied as a cancer stem cell marker in a variety of solid cancers. The functional role of CD24 is either fulfilled by combining with ligands or participating in signal transduction, which mediate the initiation and progression of neoplasms. Recently, CD24 was also described as an innate immune checkpoint with apparent significance in several types of solid cancers. Herein, we review the current understanding of the molecular fundamentals of CD24, the role of CD24 in tumorigenesis and cancer progression, the possibility as a promising therapeutic target and summarized different therapeutic agents or strategies targeting CD24 in solid cancers. Video Abstract

Sawkar Vijay Pramod,1 Ferry Safriadi,1 Bethy S Hernowo,2 Reiva Farah Dwiyana,3 Nurvita Trianasari,4 Shin Egawa5 1Department of Urology, Faculty of Medicine Universitas Padjadjaran, Hasan Sadikin Academic Medical Center, Bandung, Indonesia; 2Department of Pathology, Faculty of Medicine Universitas Padjadjaran, Hasan Sadikin Academic Medical Center, Bandung, Indonesia; 3Faculty of Medicine Universitas Padjadjaran, Bandung, Indonesia; 4Economics and Business School, Telkom University, Bandung, West Java, Indonesia; 5Department of Urology, Jikei University School of Medicine, Nishi-Shimbashi, Minato-ku, Tokyo, JapanCorrespondence: Sawkar Vijay Pramod, Department of Urology, Faculty of Medicine Universitas Padjadjaran, Hasan Sadikin Academic Medical Center, Bandung, Indonesia, Email doktervj@yahoo.co.idPurpose: To the best of our knowledge, Androgen receptor (AR) and cluster of differentiation 24 (CD24) expression in bladder urothelial carcinoma (UC) has not yet been reported in our population. The aim of this study was to evaluate the expression of both markers in UCB using immunohistochemistry.Materials and Methods: Data from 60 patients with UCB were obtained between 2009 and 2018. The samples were divided into four groups based on their smoking history. Group 1 included non-smokers, group 2 smoked < 20 cigarettes/day for 30 years, group 3 smoked for 31– 40 years, and group 4 smoked for > 40 years. Each group then divided into Non muscle invasive bladder cancer (NMIBC) and muscle invasive bladder cancer (MIBC) subgroups. The smear was stained with hematoxylin and eosin (HE) - immunohistochemistry of CD24 and RA, followed by histoscore assessment.Results: The male to female smoking rates was 1.8. Based on gender, in the NMIBC group there were 85.7% men and 14.3% were women while in MIBC 74.4% men and 25.6% women. The mean age of the NMIBC and MIBC groups was 56.3 years and 54.5 years, respectively. There was no significant relationship between smoking status in group 2 (OR 0.31, CI 95% CI, p=0,39), group 3 (OR 013, CI 95% CI, p=0,05), and group 4 (OR 0.23, CI 95% CI, p=0215) to the UCB invasiveness. A significant relationship was observed between cytoplasmic AR expression and UCB invasiveness (OR 0.14[0,04; 0.47], CI 95%, p=0.001). There was no significant relationship between RA in the nucleus and UCB invasion (OR 1.09[0,18; 6.48] CI 95%, p=1000). No significant relationship was observed between CD24 expression and UCB invasiveness (OR 0.81[0,27– 2,45] CI 95%, p=0712).Conclusion: Cytoplasmic AR expression is associated with UCB invasiveness. Smoking history and CD24 expression were not associated with UCB invasion.Keywords: androgen receptor, CD24, immunohistochemistry, smoking, urothelial carcinoma of the bladder

This article is an editorial that explores the role of CD24 in cellular development and disease. CD24 is a molecule found on various cells, including immune cells, and its glycosylation gives it diverse biological functions. It is involved in B cell development and is expressed at different stages of maturation. CD24 expression is also associated with myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) and is increased in individuals with this condition. Additionally, CD24 is expressed in solid tumors and is linked to increased metastatic potential. The article discusses the use of CD24 as a target for immunotherapy and its role in immune evasion. It highlights two review articles that explore the interactions between CD24 and Siglecs, as well as the association of CD24 with ovarian cancer. Original research articles are also mentioned, which demonstrate the contribution of CD24 expression on dendritic cells to T cell priming and the association of CD24 with B cell metabolism in ME/CFS patients. The document emphasizes the potential role of CD24 in regulating immune and metabolic processes in B cells, and the altered CD24 expression in B cells from ME/CFS patients. It also discusses the diverse functions of CD24 in immune and innate cell interactions with tumor cells and its contribution to T cell priming. The authors of the article declare no conflicts of interest, and the claims expressed in the article are solely those of the authors. [Extracted from the article]

IntroductionDisturbances of energy metabolism contribute to the clinical manifestations of myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS). Previously, we found that B cells from ME/CFS patients have an increased expression of CD24, a modulator of many cellular functions including those of cell stress. The relative ability of B cells from ME/CFS patients and healthy controls (HC) to respond to rapid changes in energy demand was compared.MethodsCD24, the ectonucleotidases CD39 and CD73, the NAD-degrading enzyme CD38, and mitochondrial mass (MM) were measured following cross-linking of the B cell receptor and costimulation with either T-cell-dependent or Toll-like-receptor-9-dependent agonists. The levels of metabolites consumed/produced were measured using 1H-NMR spectroscopy and analyzed in relation to cell growth and immunophenotype.ResultsProliferating B cells from patients with ME/CFS showed a lower mitochondrial mass and a significantly increased usage of essential amino acids compared with those from HC, with a significantly delayed loss of CD24 and an increased expression of CD38 following stimulation.DiscussionThe immunophenotype results suggested the triggering of a stress response in ME/CFS B cells associated with the increased usage of additional substrates to maintain necessary ATP levels. Disturbances in energy metabolism in ME/CFS B cells were thus confirmed in a dynamic in vitro model, providing the basis for further mechanistic investigations.

CD47 and its receptor signal regulatory protein α (SIRPα) act as a dominant antiphagocytic, “don’t eat me” signal. Recent studies reveal CD24 as a novel target for cancer immunotherapy by macrophages in ovarian cancer and breast cancer. However, whether simultaneous blockade of CD47 and CD24 by a bispecific antibody may result in a potential synergy is still unclear. In the present study, we for the first time designed and developed a bispecific antibody fusion protein, PPAB001 for cotargeting CD47 and CD24. Data demonstrate that simultaneous blockade of CD47/SIRPα and CD24/Siglec-10 signaling by PPAB001 potently promoted macrophage phagocytosis of tumor cells. Compared to single CD47 or CD24 targeting agents, PPAB001 was more effective in inhibiting tumor growth in both mouse 4T-1 syngeneic and human SK-OV-3 xenogeneic tumor models. Mechanistically, we found that PPAB001 therapy markedly increased the proportion of tumor-infiltrating macrophages and upregulated interleukin-6 and tumor necrosis factor-α levels that were representative macrophage inflammatory cytokines. Notably, an increased ratio of M1/M2 in tumor-infiltrating macrophages in the mice treated with PPAB001 suggested that the dual blockade may promote the transition of macrophages from M2 to M1. Taken together, our data supported the development of PPAB001 as a novel immunotherapeutic in the treatment of CD47 and CD24 double-positive cancers.

ABSTRACTObjective: Multiple Myeloma (MM) is a hematologic malignant disease with unclear molecular mechanisms. This integrated bioinformatic study aimed to identify key genes, pathways and immune cell infiltration pattern in MM.Methods: Differentially expressed genes (DEGs) from GSE6477 and GSE16558 dataset were filtrated with R package ‘limma’, whose function were explored by Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis. The key genes were selected from Protein–protein interaction network (PPI) and logistic regression model. The correlation between key genes and survival in MM was evaluated using the survival and survminer package. Additionally, immune filtration analysis was accomplished by CIBERSORT tools.Results: 118 DEGs (92 up-regulated and 26 down-regulated) from two GSE datasets were identified, which were closely related with B cell receptor signaling pathway and Epstein-Barr virus infection. Furthermore, CD24 and PTPRC of five hub genes identified in PPI network were further screened out by the logistic regression model. Besides, CD24 and PTPRC expression were significantly correlated to the survival time in MM patients. Finally, MM might cause different infiltrating immune cell compositions, including increased infiltrations of B cells memory, Plasma cells, T cells CD4 memory resting, T cells follicular helper, Tregs, NK cells resting, Macrophages(M0/M1), Dendritic cells resting and Mast cells activating, and lower proportions of B cells naïve, T cells CD4 naïve, Macrophages M2 and Neutrophils.Conclusion: Targeting CD24 and PTPRC as molecular markers of MM is valuable to MM therapy. Moreover, the immune cell infiltration will provide new insights into MM immunopathology.

Cluster of differentiation 24 (CD24), a mucin-like highly glycosylated molecule has been extensively studied as a cancer stem cell marker in a variety of solid cancers. The functional role of CD24 is either fulfilled by combining with ligands or participating in signal transduction, which mediate the initiation and progression of neoplasms. Recently, CD24 was also described as an innate immune checkpoint with apparent significance in several types of solid cancers. Herein, we review the current understanding of the molecular fundamentals of CD24, the role of CD24 in tumorigenesis and cancer progression, the possibility as a promising therapeutic target and summarized different therapeutic agents or strategies targeting CD24 in solid cancers. 7wFofkUxGk2QGv4c1Qdt8b Video Abstract [ABSTRACT FROM AUTHOR]

Alternative therapeutic options targeting urologic malignancies, such as germ cell tumours, as well as urothelial, renal and prostate carcinomas, are still urgently needed. The membrane protein CD24 represents a promising immunotherapeutical approach. The present study aimed to decipher the molecular function of CD24 in vitro and evaluate the cytotoxic capacity of a third‐generation natural killer (NK) cell chimeric antigen receptor (CAR) against CD24 in urologic tumour cell lines. Up to 20 urologic tumour cell lines and several non‐malignant control cells were included. XTT viability assays and annexin V/propidium iodide flow cytometry analyses were performed to measure cell viability and apoptosis rates, respectively. Co‐immunoprecipitation followed by mass spectrometry analyses identified direct interaction partners of CD24. Luciferase reporter assays were used to functionally validate transactivation of CD24 expression by SOX2. N‐ and O‐glycosylation of CD24 were evaluated by enzymatic digestion and mass spectrometry. The study demonstrates that SOX2 transactivates CD24 expression in embryonal carcinoma cells. In cells of different urological origins, CD24 interacted with proteins involved in cell adhesion, ATP binding, phosphoprotein binding and post‐translational modifications, such as histone acetylation and ubiquitination. Treatment of urological tumour cells with NK‐CD24‐CAR cells resulted in a decreased cell viability and apoptosis induction specifically in CD24+ tumour cells. Limitations of the study include the in vitro setting, which still has to be confirmed in vivo. In conclusion, we show that CD24 is a promising novel target for immune therapeutic approaches targeting urologic malignancies. [ABSTRACT FROM AUTHOR]

Cancer immunotherapy strategies are based on the utilization of immune checkpoint inhibitors to instigate an antitumor immune response. The efficacy of immune checkpoint blockade, directed at adaptive immune checkpoints, has been demonstrated in select cancer types. However, only a limited subset of patients has exhibited definitive outcomes characterized by a sustained response after discontinuation of therapy. Recent investigations have highlighted the significance of immune checkpoint molecules that are overexpressed in cancer cells and inhibit myeloid lineage immune cells within a tumor microenvironment. These checkpoints are identified as potential targets for anticancer immune responses. Notably, the immune checkpoint molecules CD24 and CD200 have garnered attention owing to their involvement in tumor immune evasion. CD24 and CD200 are overexpressed across diverse cancer types and serve as signaling checkpoints by engaging their respective receptors, Siglec-10 and CD200 receptor, which are expressed on tumor-associated myeloid cells. In this review, we summarized and discussed the latest advancements and insights into CD24 and CD200 as emergent immune checkpoint moieties, further delving into their therapeutic potentials for cancer treatment. [ABSTRACT FROM AUTHOR]

Objectives Pleural mesothelioma is a rapidly progressing pleural neoplasm caused by asbestos exposure of a long latency around 30-40 years. Patients with mesothelioma are usually diagnosed at a late stage with poor outcomes in terms of morbidity and mortality with 6–12 months' median survival. Despite the prohibited use of asbestos, malignant pleural mesothelioma is still increasingly being occurred in young age and female patients. Different un-standardized biomarkers have been used to diagnose MPM as mesothelin and febulin with controversial results, so we used CD 24 as a biomarker to diagnose and differentiate between different subtypes of malignant pleural mesothelioma. Materials and methods Our cohort study included total of fifty-nine patients with exudative pleural effusion. All patients underwent full history taking, clinical examination, blood tests (CBC, coagulation profile, liver and kidney functions), tapping of pleural effusion and to send pleural fluid investigations for LDH, albumin, total protein and albumin, then confirmed exudative pleural effusion patients were subjected to thoracic ultrasonography and medical thoracoscopy for the majority of cases or ultrasound guided biopsy in selected cases to obtain pleural biopsies for histopathology and then the examination of pleural biopsies for CD24 expression. Results Our study demonstrated the possibility of using CD24 as a biomarker in the immunostaining of pleural biopsies to differentiate between malignant pleural mesothelioma and pleural malignancy other than mesothelioma (18 mesothelioma cases versus 2 nonmesothelioma malignant cases) with high statistical significance P value < 0.001 and also it can discriminate between subtypes of mesothelioma as it showed marked significance in epithelioid subtype (12 epithelioid versus 1 sarcomatoid versus 5 biphasic subtypes) with more uptake by score +2 in epithelioid mesothelioma. Conclusions CD24 can be supposed to be a routine biomarker for immunohistochemistry of pleural tissue samples in diagnosis of mesothelioma and it can be used to differentiate between subtypes of malignant mesothelioma subtypes. [ABSTRACT FROM AUTHOR]

Breast cancer (BRCA) is the most diagnosed cancer worldwide and is responsible for the highest cancer-associated mortality among women. It is evident that anoikis resistance contributes to tumour cell metastasis, and this is the primary cause of treatment failure for BRCA. However, anoikis-related gene (ARG) expression profiles and their prog- nostic value in BRCA remain unclear. In this study, a prognostic model of ARGs based on The Cancer Genome Atlas (TCGA) database was established using a least absolute shrinkage and selection operator analysis to evaluate the prognostic value of ARGs in BRCA. The risk factor graph demonstrated that the low-risk group had longer survival than the high-risk group, implying that the prognostic model had a good performance. We identified 11 ARGs that exhibited differential expression between the two risk groups in TCGA and Gene Expression Omnibus databases. Through Gene Ontology and Kyoto Encyclopaedia of Genes and Genomes enrichment analyses, we revealed that the screened ARGs were associated with tumour progression and metastasis. In addition, a protein-protein interaction network showed potential interactions among these ARGs. Furthermore, gene set enrichment analysis suggested that the Notch and Wnt signalling pathways were overexpressed in the high-risk group, and gene set variation analysis revealed that 38 hallmark genes differed between the two groups. Moreover, Kaplan-Meier survival curves and receiver operating characteristic curves were used to identify five ARGs (CD24, KRT15, MIA, NDRG1, TP63), and quantitative polymerase chain reaction was employed to assess the differential expression of these ARGs. Univariate and multivariate Cox regression analyses were then performed for the key ARGs, with the best prediction of 3 year survival. In conclusion, ARGs might play a crucial role in tumour progression and serve as indicators of prognosis in BRCA. [ABSTRACT FROM AUTHOR]

BACKGROUND: The combination of nanotechnology and medicine has opened up a new path in the field of selective targeting and tumor treatment. Through the application of nano carriers, the targeted delivery and stability of loaded drugs are ensured, and the cell uptake and biocompatibility are enhanced. OBJECTIVE: To prepare a glutathione and pH double-responsive CD24 aptamer-modified nanodrug delivery system PC (coBP) Ca for ferroptosis agonists Erastin and biplasmids and to investigate its precise targeting and feasibility of CD24 highly expressed cells in triple negative breast cancer in vitro. METHODS: PEG-CAPDB underwent multiple polymerization reactions to form a nanosphere skeleton called: COOH-PEG-CPADB-[co BMA co PDSMA], and then PC (coBP) formation by self-assembling synthesis of the internally loaded ferroptosis agonist Erastin, 1-2M2ge compound, NF2 knockout plasmid and YAP overexpressed plasmid. SELEX technology was used to screen CD24 aptamers to further modify PC (CoBP). Nano-drug delivery system PC (coBP) Ca was eventually formed. The effects of CD24 aptamer modification on the surface of PC(coBP)Ca, sensitivity to glutathione and pH, phagocytosis and targeting properties of immune cells escaping, lysosomal escaping phagocytosis and drug burst release properties, and phagocytosis of phagocytes were detected. RESULTS AND CONCLUSION: The average particle size of PC (coBP) Ca was (141.11±13.43) nm. The average polydispersity index was (0.353±0.074). The average Zeta potential showed good dispersibility. The average drug loading of Erastin was (23.34±2.45)%. The encapsulation rate of PC (coBP) Ca was (90.24±3.11)%, and the 4-hour release was about 90% under the dual response system of glutathione and pH, which could effectively evade immune cell phagocytosis to accurately target CD24 highly expressed triple negative breast cancer, escape lysosomes, then achieve drug release, which activates the ferroptosis pathway and promotes phagocyte phagocytosis. The successful synthesis of nano-delivery system PC (coBP) Ca has the characteristics of precision, effectiveness, safety and low toxicity, and is expected to become a CD24 high-expression cell-targeted nano-delivery system in triple negative breast cancer. [ABSTRACT FROM AUTHOR]

Rationale: Acute respiratory distress syndrome (ARDS) is a major global health concern with a significant unmet need. EXO-CD24 is delivered via inhalation-reduced cytokines and chemokine secretion and lung injury in ARDS and improved survival in mice models of ARDS, influenza, and sepsis. Objectives: This clinical paper aims to evaluate the potential of EXO-CD24, a novel immunomodulatory treatment, in the compassionate care of critically ill, intubated patients with post-infection-induced acute respiratory distress syndrome (ARDS). Methods: Eleven critically ill patients diagnosed with post-infection ARDS (10 with COVID-19 and one with an adenovirus-associated infection) were administered EXO-CD24 in four medical centers across Israel. The patients had multiple co-morbidities, including cancer, hypertension, diabetes, and ischemic heart disease, and met the criteria for severe ARDS according to the Berlin classification. EXO-CD24 was administered via inhalation, and adverse events related to its use were carefully monitored. Measurements and Main Results: The administration of EXO-CD24 did not result in any recorded adverse events. The median hospitalization duration was 11.5 days, and the overall mortality rate was 36%. Notably, patients treated at the Tel Aviv Medical Center (TASMC) showed a lower mortality rate of 12.5%. The WBC and CRP levels decreased in comparison to baseline levels at hospitalization, and rapid responses occurred even in patients with kidney transplants who were off the ventilator within a few days and discharged shortly thereafter. The production of cytokines and chemokines was significantly suppressed in all patients, including those who died. Among the patients at TASMC, four had kidney transplants and were on immunosuppressive drugs, and all of them fully recovered and were discharged from the hospital. Conclusions: EXO-CD24 holds promise as a potential therapeutic agent for all stages of ARDS, even in severe intubated cases. Importantly, EXO-CD24 demonstrated a favorable safety profile without any apparent side effects with promising efficacy. Furthermore, the potential of EXO-CD24 as a platform for addressing hyper-inflammatory states warrants exploration. Further research and larger-scale clinical trials are warranted to validate these preliminary findings. [ABSTRACT FROM AUTHOR]

Background: Triple-negative breast cancer (TNBC) is an aggressive subtype with the most unfavorable clinical outcomes, in part due to tumor heterogeneity, treatment resistance, and tumor relapse. The TNBC subtypes [basal-like 1 (BL1), basal-like 2 (BL2), mesenchymal (M), and luminal androgen receptor (LAR)] are biologically and clinically distinct entities that respond differently to local and systemic therapies. Therefore, we need to have a better understanding of cancer stemness relating to drug-resistant populations in the TNBC subtypes.Methods: Breast cancer stem cell (BCSC) distribution was investigated using an integrated flow cytometry approach with the ALDEFLUOR™ assay (ALDH) and CD24/CD44 antibodies. In total, 27 commercially available cell lines derived from normal and malignant mammary tissue were characterized into differentiated tumor cells and/or BCSC subpopulations (ALDH−CD44+CD24-/low enriched mesenchymal-like BCSCs, ALDH+non-CD44+CD24−/low enriched epithelial-like BCSCs, and highly purified ALDH+CD44+CD24−/low BCSCs).Results: BCSCs were not only enriched in estrogen receptor (ER) negative (mean, 49.6% versus 6.9% in ER+) and TNBC cell lines (51.3% versus 2.1% in Luminal A), but certain BCSC subpopulations (e.g., enriched mesenchymal-like BCSCs) were also significantly more common in the M (64.0% versus 6.2% in BL1; 64.0% versus 0% in LAR) and BL2 (77.4% versus 6.2% in BL1; 77.4% versus 0% in LAR; 77.4% versus 10.4% in TNBC UNS) TNBC subtypes. In contrast, ALDH status alone was not indicative of ER status or BC subtype.Conclusion: Taken together, these findings demonstrate the enrichment of potentially treatment-resistant BCSC subpopulations in the M and BL2 triple-negative breast cancer subtypes.

Introduction: Glioblastoma (GBM) is the most invasive type of glioma, is insensitive to radiotherapy and chemotherapy, and has high proliferation and invasive ability, with a 5-year survival rate of <5%. Cuproptosis-related genes (CRGs) have been successfully used to predict the prognosis of many types of tumors. However, the relationship between cuproptosis and GBM remains unclear. Methods: Here, we sought to identify CRGs in GBM and elucidate their role in the tumor immune microenvironment and prognosis. To that aim, changes in CRGs in The Cancer Genome Atlas (TCGA) transcriptional and Gene Expression Omnibus (GEO) datasets (GEO4290 and GEO15824) were characterized, and the expression patterns of these genes were analyzed. Results: A risk score based on CRG expression characteristics could predict the survival and prognosis of patients with GBM and was significantly associated with immune infiltration levels and the expression of CD47 and CD24, which are immune checkpoints of the “don't eat me “signal. Furthermore, we found that the CDKN2A gene may predict GBM sensitivity and resistance to drugs. Discussion: Our findings suggest that CRGs play a crucial role in GBM outcomes and provide new insights into CRG-related target drugs/molecules for cancer prevention and treatment. [ABSTRACT FROM AUTHOR]

Hepatocellular carcinoma (HCC) is a prevalent and lethal disease, and tumor regression rarely occurs in advanced HCC patients due to limited effective therapies. Given the enrichment of macrophages in HCC and their role in tumor immunity, transforming them into chimeric antigen receptor macrophages (CAR-Ms) is thought to increase HCC cell-directed phagocytosis and tumoricidal immunity. To test this hypothesis, mRNA encoding CAR is encapsulated in a lipid nanoparticle (LNP) that targets liver macrophages. Notably, the LNPs adsorb specific plasma proteins that enable them to target HCC-associated macrophages. Moreover, mRNA encoding Siglec-G lacking ITIMs (Siglec-GΔITIMs) is codelivered to liver macrophages by LNP to relieve CD24-mediated CAR-Ms immune suppression. Mice treated with LNPs generating CAR-Ms as well as CD24-Siglec-G blockade significantly elevate the phagocytic function of liver macrophages, reduce tumor burden and increase survival time in an HCC mouse model. Arguably, our work suggests an efficacious and flexible strategy for the treatment of HCC and warrants further rigorous evaluation in clinical trials. Lipid nanoparticle-mediated dual mRNA co-delivery for in situ generation of Siglec-GΔITIMs-expressing GPC3-specific CAR macrophages augments hepatocellular carcinoma immunotherapy. [Display omitted] • Dual mRNA co-laden lipid nanoparticle was developed for in situ macrophage reprogramming. • LNP-engineered CAR-macrophage exhibited GPC3-specific tumor phagocytosis. • Siglec-GΔITIMs mRNA co-engineering further enhanced the antitumor efficacy of CAR macrophage. [ABSTRACT FROM AUTHOR]

The "do not eat me" signaling pathway is extremely active in tumor cells, providing a means for these cells to elude macrophage phagocytosis and escape immune surveillance. Representative markers of this pathway, such as CD47 and CD24, are highly expressed in numerous tumors. The interaction of SIRPα with CD47 reduces the accumulation of non-myosin ⅡA on the cell membrane. The combination of CD24 and Siglec10 ultimately leads to the recruitment of SHP-1 or SHP-2 to reduce signal transduction. Both of them weaken the ability of macrophages to engulf tumor cells. Blocking the mutual recognition between CD47-SIRPα or CD24-Siglec10 using large molecular proteins or small molecular drugs represents a promising avenue for tumor immunotherapy. Doing so can inhibit signal transduction and enhance macrophage clearance rates of cancer cells. In this paper, we summarize the characteristics of the drugs that affect the "do not eat me" signaling pathway via classical large molecular proteins and small molecule drugs, which target the CD47-SIRPα and CD24-Siglec10 signaling pathways, which target the CD47-SIRPα and CD24-Siglec10 signaling pathways. We expect it will offer insight into the development of new drugs centered on blocking the "do not eat me" signaling pathway. [ABSTRACT FROM AUTHOR]

Acute kidney injury (AKI) is characterized by cell death and inflammation. CD24 is a protein induced during tissue damage and is not expressed in mature renal tissue. We explored the role of CD24 in the pathogenesis of folic acid-induced AKI (FA-AKI) in mice. A single Intraperitoneal (IP) injection of folic acid induced AKI in WT and CD24−/− mice. Renal function tests, histological analysis, immunohistochemistry, Western blot analysis, and ELISA were performed to assess the severity of renal damage and the intensity of the inflammatory response. FA-AKI induced CD24 in the distal tubular epithelial cells. Compared to WT mice, FA-AKI CD24−/− mice exhibited an attenuated reduction in renal function and histological injury, lower serum IL-10 and interferon γ, and decreased expression of renal TNFα. In contrast, renal and systemic IL-33 upregulation were augmented. CD24−/− FA-AKI animals exhibited increased splenic margination and renal infiltration of regulatory T cells (Tregs). At day 7, FA-AKI CD24−/− mice exhibited increased expression of tubular pro-apoptotic and decreased anti-apoptotic proteins compared to WT animals. Anti-CD24 antibody administration to FA-AKI mice attenuated the decrease in renal function as well as the histological injury. Renal biopsies from patients with ATN stained strongly for CD24 in the distal tubules. In conclusion, during AKI, upregulation of CD24 promotes renal inflammation through inhibition of Treg infiltration and diversion of cell death towards necrosis rather than apoptosis. Neutralization of CD24 may prove a target for future therapies in AKI. [ABSTRACT FROM AUTHOR]

CD24 is a glycosylphosphatidylinositol linked molecular which expressed in diverse malignant tumor cells, particular in ovarian carcinoma cells and ovarian carcinoma stem cells. The CD24 expression is associated with increased metastatic potential and poor prognosis of malignancies. CD24 on the surface of tumor cells could interact with Siglec-10 on the surface of immune cells, to mediate the immune escape of tumor cells. Nowadays, CD24 has been identified as a promising focus for targeting therapy of ovarian cancer. However, the roles of CD24 in tumorigenesis, metastasis, and immune escape are still not clearly demonstrated systematically. In this review, we i) summarized the existing studies on CD24 in diverse cancers including ovarian cancer, ii) illustrated the role of CD24-siglec10 signaling pathway in immune escape, iii) reviewed the existing immunotherapeutic strategies (targeting the CD24 to restore the phagocytic effect of Siglec-10 expressing immune cells) based on the above mechanisms and evaluated the priorities in the future research. These results might provide support for guiding the CD24 immunotherapy as the intervention upon solid tumors. [ABSTRACT FROM AUTHOR]