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Background: This study explores the significance of computed tomography (CT) radiomic features, along with inflammation and nutrition biomarkers, in the prognosis of postoperative patients with T3N0M0 esophageal squamous cell carcinoma (ESCC). The study aims to construct a related nomogram. Methods: A total of 114 patients were enrolled and randomly assigned to training and validation cohorts in a 7:3 ratio. Radiomic features were extracted from their preoperative chest‐enhanced CT arterial images of the primary tumor, and inflammatory and nutritional indices, including neutrophil‐to‐lymphocyte ratio (NLR), lymphocyte‐to‐monocyte ratio (LMR), platelet‐to‐lymphocyte ratio (PLR), systemic immune‐inflammation index (SII), and prognostic nutritional index (PNI), were calculated based on laboratory data from the 3 days before surgery. Intra‐class correlations coefficient (ICC) and least absolute shrinkage and selection operator (Lasso) were applied to screen valuable radiomics features predicting overall survival (OS), and the Rad‐score was calculated. In the training cohort, univariate and multivariate Cox regression analyses identified independent prognostic factors, which were adopted to establish the nomogram. Results: Eight radiomic features were selected for Rad‐score calculation. Multivariate Cox regression revealed Rad‐score, PNI, NLR, and PLR as independent prognostic factors for ESCC patients (p < 0.05). A nomogram was constructed based on these variables. The concordance index (C‐index) for the nomogram was 0.797 (95% CI: 0.726–0.868) in the training cohort and 0.796 (95% CI: 0.702–0.890) in the validation cohort. Calibration curves indicated good calibration ability, and the receiver operating characteristic (ROC) analysis demonstrated superior discriminative ability for the nomogram in comparison to the Rad‐score alone. Decision curve analysis (DCA) confirmed the clinical utility of the nomogram. Conclusion: We developed and validated a nomogram for predicting the OS of postoperative T3N0M0 ESCC patients, integrating nutritional, inflammatory markers, and radiomic signature. The combined nomogram can serve as a robust tool for risk stratification and clinical management. [ABSTRACT FROM AUTHOR]

BACKGROUND: Gastric cancer (GC) is one of the most common tumors. There were several classifications of GC recently. The value of Lauren classification in evaluating the prognosis after radical gastrectomy was still unclear and the prognosis of gastric cancer remained relatively poor in the absence of prognostic biomarkers. This study aimed to explore microRNA (miRNA) in the prognosis of GC with different Lauren classification. METHODS: A retrospective study of 1144 patients was performed in this study. Quantificational reverse transcription-PCR (qRT-PCR) was used to examine the expression of miRNAs. Univariate and multivariate analysis were performed to evaluate prognosis value of Lauren classification. RESULTS: Total 1144 GC patients were recruited in this cohort, including 302 diffuse type (26.4%), 436 intestinal type (38.1%) and 406 mixed type (35.5%) GC. Multivariate analysis showed that Lauren classification, patients' age, tumor size, tumor infiltrating depth, vascular nerve infiltrating and metastatic lymph nodes ration were significantly correlated with GC patients' OS and DFS. The miR-141-3p, miR-200b-3p and miR-133a-5p were significantly down-regulated in diffuse type compared to intestinal type GC tissues, the miR-105-5p had significant lower expression in diffuse type compared with intestinal type and mixed type GC tissues. As a consequence of univariate analysis, low miR-141-3p in diffuse type GC showed significant worse OS and DFS than high miR-141-3p. CONCLUSIONS: Lauren classification was an independent prognostic factor in GC. MiR-141-3p was an independent prognostic factor and a promising prognostic biomarker in Lauren classification GC. [ABSTRACT FROM AUTHOR]

Immune checkpoint blockade (ICB) has demonstrated curative potential in several types of cancer, but only for a small number of patients. Thus, the identification of reliable and noninvasive biomarkers for predicting ICB responsiveness is an urgent unmet need. Here, we show that ICB increased tumor vessel perfusion in treatment-sensitive EO771 and MMTV- PyVT breast tumor as well as CT26 and MCA38 colon tumor models, but not in treatment-resistant MCaP0008 and 4T1 breast tumor models. In the sensitive tumor models, the ability of anti-cytotoxic T lymphocyte-associated protein 4 or anti-programmed cell death 1 therapy to increase vessel perfusion strongly correlated with its antitumor efficacy. Moreover, globally enhanced tumor vessel perfusion could be detected by Doppler ultrasonography before changes in tumor size, which predicted final therapeutic efficacy with more than 90% sensitivity and specificity. Mechanistically, [CD8.sup.+] T cell depletion, IFN-[gamma] neutralization, or implantation of tumors in IFN-[gamma] receptor knockout mice abrogated the vessel perfusion enhancement and antitumor effects of ICB. These results demonstrated that ICB increased vessel perfusion by promoting [CD8.sup.+] T cell accumulation and IFN-[gamma] production, indicating that increased vessel perfusion reflects the successful activation of antitumor T cell immunity by ICB. Our findings suggest that vessel perfusion can be used as a novel noninvasive indicator for predicting ICB responsiveness., Introduction Recent advances in cancer immunotherapy have revolutionized cancer treatment. Immune checkpoint blockade (ICB), designed to target immune suppressive signals such as cytotoxic T lymphocyte-associated protein 4 (CTLA4) or programmed [...]

Objective: Radiation‐induced skin injury (RISI) remains a serious concern during radiotherapy. IL‐10 is considered as an immune suppressive cytokine by inhibiting the secretion of the proinflammatory cytokines in cells. The aim of this study was to evaluate the protective role of Erb (IL10) 2 against ionizing radiation. Methods: We fused Interleukin 10 (IL‐10) dimer onto an anti‐epidermal growth factor receptor antibody Cetuximab (Erbitux) to form a new bispecific protein Erb‐(IL10)2. The protective effect and biological activity of Erb‐(IL10)2 was measured in model of RISI. Results: Under the condition of 20 Gy irradiation, surviving cells in the IR group decreased significantly compared with the non‐IR group (p = 0.0021). The survival rates of HaCaT (p = 0.0038) and WS1 (p = 0.0003) cells were significantly increased after IL‐10 treatment. The apoptosis rates of HaCaT (p = 0.0048) and WS1 (p = 0.0074) cells in the IL‐10 group were significantly lower compared to the NC group. Under 20 Gy irradiation conditions, IL‐10 fusion protein reduced the level of reactive oxygen in HaCaT (p = 0.0046) and WS1 (p<0.0001) cells compared to the control group. Relatively normal granular mitochondrial morphology was observed in the IL‐10 group after 20 Gy X‐ray irradiation compared with the NC group. Ater 35 Gy electron radiation, the levels of reactive oxygen species in the skin tissue of C57/B6 mice injected with IL‐10 fusion protein were significantly lower than those in the PBS group (p = 0.001). Compared with the PBS group and the other IL‐10 groups, the group treated with 0.2 mg/kg IL‐10 showed a significant decrease in MDA level (p = 0.0024). Compared with the PBS group, the thickness of the stratum corneum in groups treated with 0.05, 0.1 and 0.2 mg/kg IL‐10 decreased, and the skin appendages were well‐preserved. In the group treated with 0.2 mg/kg IL‐10, the skin tissue structure was still relatively intact, and the masson staining area was smaller than that of the PBS group. Conclusion: IL‐10 plays a role in inhibiting radioactive fibrosis in radioactive skin injury. IL‐10 has a protective effect on skin cell damage after ionizing radiation irradiation both in vitro and in vivo. Moreover, IL‐10 plays a role in inhibiting radioactive fibrosis in radioactive skin injury. [ABSTRACT FROM AUTHOR]

Purpose: Positron emission tomography (PET) with specific diagnostic probes for quantifying CD8+ T cells has emerged as a powerful technique for monitoring the immune response. However, most CD8+ T cell radiotracers are based on antibodies or antibody fragments, which are slowly cleared from circulation. Herein, we aimed to develop and assess 68 Ga-NODAGA-SNA006 for instant PET (iPET) imaging of CD8+ T cells. Methods: A novel nanobody without a hexahistidine (His6) tag, SNA006-GSC, was designed, site-specifically conjugated with NODAGA-maleimide and radiolabelled with 68 Ga. The PET imaging profiles of 68 Ga-NODAGA-SNA006 were evaluated in BALB/c MC38-CD8+/CD8− tumour models and cynomolgus monkeys. Three volunteers with lung cancer underwent whole-body PET/CT imaging after 68 Ga-NODAGA-SNA006 administration. The biodistribution, pharmacokinetics and dosimetry of patients were also investigated. In addition, combined with immunohistochemistry (IHC), the quantitative performance of the tracer for monitoring CD8 expression was evaluated in BALB/c MC38-CD8+/CD8− and human subjects. Results: 68 Ga-NODAGA-SNA006 was prepared with RCP > 98% and SA > 100 GBq/μmol. 68 Ga-NODAGA-SNA006 exhibited specific uptake in MC38-CD8+ xenografts tumours, CD8-rich tissues (such as the spleen) in monkeys and CD8+ tumour lesions in patients within 1 h. Fast washout from circulation was observed in three volunteers (t1/2 < 20 min). A preliminary quantitative linear relationship (R2 = 0.9668, p < 0.0001 for xenografts and R2 = 0.7924, p = 0.0013 for lung patients) appeared between 68 Ga-NODAGA-SNA006 uptake and CD8 expression. 68 Ga-NODAGA-SNA006 was well tolerated by all patients. Conclusion: 68 Ga-NODAGA-SNA006 PET imaging can instantly quantify CD8 expression with an ideal safety profile and is expected to be important for dynamically tracking CD8+ T cells and monitoring immune responses for individualised cancer immunotherapy. Trial registration: NCT05126927 (19 November 2021, retrospectively registered). [ABSTRACT FROM AUTHOR]

Objective: Although radiotherapy (RT) has been widely used in cancer treatment, it provides limited benefits in patients with metastatic cancers due to rare abscopal antitumor effects. Recent progress in cancer immunotherapy provides a potential new strategy to boost the abscopal antitumor effects of RT. Methods: We fused interleukin 10 (IL10) dimer onto the anti‐epidermal growth factor receptor antibody cetuximab (Erbitux) to form a new bispecific protein Erb‐(IL10)2. The antitumor effect and biological activity of Erb‐(IL10)2 were measured in the B16‐EGFR‐OVA tumor model. In vivo cell depletion and flow cytometry analyses were used to assess the mechanism of antitumor effects. Results: Erb‐(IL10)2 treatment alone showed modest tumor growth inhibition, while local single dose RT (10 Gy) retarded irradiated tumor growth without affecting the growth of nonirradiated tumors. Notably, the combination therapy of RT and Erb‐(IL10)2 not only additively inhibited irradiated tumor growth but also induced abscopal antitumor responses. In vivo depletion of CD8+ T cells abrogated the combinational antitumor effects, while blocking lymphocyte trafficking through FTY720 treatment abolished the abscopal antitumor responses without affecting the antitumor effects on the irradiated tumor sites. Conclusion: This study provides evidence for the radiosensitive role of Erb‐(IL10)2 in the B16‐EGFR‐OVA tumor model. Our findings suggest a novel strategy to elicit the abscopal antitumor effects of RT by combining tumor‐targeted therapy with IL10. [ABSTRACT FROM AUTHOR]

Immune checkpoint blockade (ICB) has shown long‐term survival benefits, but only in a small fraction of cancer patients. Recent studies suggest that improved vessel perfusion by ICB positively correlates with its therapeutic outcomes. However, the underlying mechanism of such a process remains unclear. Here, we show that anti‐cytotoxic T‐lymphocyte‐associated protein 4 (CTLA4) treatment‐induced tumor vessel normalization was accompanied by an increased infiltration of eosinophils into breast tumors. Eosinophil accumulation was positively correlated with the responsiveness of a breast tumor to anti‐CTLA4 therapy. Depletion of eosinophils subsequently negated vessel normalization, reduced antitumor immunity and attenuated tumor growth inhibition by anti‐CTLA4 therapy. Moreover, intratumoral accumulation of eosinophils relied on T lymphocytes and interferon γ production. Together, these results suggest that eosinophils partially mediate the antitumor effects of CTLA4 blockade through vascular remodeling. Our findings uncover an unidentified role of eosinophils in anti‐CTLA4 therapy, providing a potential new target to improve ICB therapy and to predict its efficacy. What's new? Immune checkpoint blockade (ICB) confers long‐term survival benefits, but only in a minority of cancer patients. Improved tumor blood vessel perfusion under ICB positively correlates with its therapeutic outcomes, but the underlying mechanisms remain unclear. Here, the authors found that anti‐CTLA4 therapy increased tumor‐associated eosinophils in breast tumor models, which correlated with tumor vessel normalization and therapeutic efficacy. In vivo depletion of eosinophils abrogated the effect of anti‐CTLA4 therapy on tumor vessels and compromised antitumor immune responses. The findings uncovered an unidentified role of eosinophils in anti‐CTLA4 therapy, providing a potential new target to improve ICB therapy and to predict its efficacy. [ABSTRACT FROM AUTHOR]

Objective: Cancer stem cells are self-renewal cells in tumors and can produce heterogeneous tumor cells, which play an important role in the development of lung squamous cell carcinoma (LSCC). In our research, we aimed to explore the expression of genes related to LSCC stem cells.Methods: We downloaded the RNAseq data, the pathological and prognostic profiles of LSCC cases from the public database TCGA. The mRNA expression-based stiffness index (mRNAsi) of LSCC was calculated and the prognostic value of mRNAsi was discussed. Then, we constructed a weighted gene co-expression network analysis (WGCNA) to screen key genes related to mRNAsi of LSCC.Results: MRNAsi is an independent prognostic factor in LSCC. We screened 5 key genes (BUB1, BIRC5, CCNB2, KIF15 and SPAG5) related to mRNAsi of LSCC based on WGCNA. The key genes were highly expressed in the tumor samples compared to the normal samples. In addition, there is a strong interaction between proteins of these key genes and a strong co-expression relationship at the transcriptional level.Conclusions: To conclude, mRNAsi play an important role in LSCC. Five key genes (BUB1, BIRC5, CCNB2, KIF15 and SPAG5) related to mRNAsi were screened, which may act as therapeutic targets for inhibiting the stem cell characteristics of LSCC. [ABSTRACT FROM AUTHOR]