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Mast cells (MCs) are bone-marrow-derived haematopoietic cells that are widely distributed in human tissues. When activated, they will release tryptase, histamine and other mediators that play major roles in a diverse array of diseases/disorders, including allergies, inflammation, cardiovascular diseases, autoimmune diseases, cancers and even death. The multiple pathological effects of MCs have made their stabilizers a research hotspot for the treatment of related diseases. To date, the clinically available MC stabilizers are limited. Considering the rapidly increasing incidence rate and widespread prevalence of MC-related diseases, a comprehensive reference is needed for the clinicians or researchers to identify and choose efficacious MC stabilizers. This review analyzes the mechanism of MC activation, and summarizes the progress made so far in the development of MC stabilizers. MC stabilizers are classified by the action mechanism here, including acting on cell surface receptors, disturbing signal transduction pathways and interfering exocytosis systems. Particular emphasis is placed on the clinical applications and the future development direction of MC stabilizers. [ABSTRACT FROM AUTHOR]

Triple negative breast cancer (TNBC) is a heterogenous disease that disproportionately affects Black women. TNBC outcomes among Black women are dismal secondary to multiple factors, such as poor healthcare accessibility resulting in delays in diagnosis, and aggressive disease biology in addition to a pro-tumor immune microenvironment (TME). Black women with breast cancer exhibit elevated levels of serum pro-inflammatory cytokines, and a pro-tumorigenic TME with higher immunosuppressive regulatory T cells (Tregs), M2 macrophages and exhausted CD8+ T cells. We have shown that the combined use of toll-like receptor 3 (TLR3) ligands with interferon-α (chemokine modulation: CKM) is able to enrich the tumor with CD8+ T cells, while not increasing immunosuppressive cells. Recent clinical trials have revealed the efficacy of immune checkpoint inhibitors (ICI) in rejuvenizing exhausted CD8+ T cells. We hypothesize that strategies to modulate the TME by enriching chemokines that attract CD8+T cells followed by reversal of CD8+ T cell exhaustion (ICI), when added to standard treatment, could potentially improve clinical outcomes, and mitigate the racial disparities in TNBC outcomes between Black and White Women. [ABSTRACT FROM AUTHOR]

The majority of patients with thyroid cancer can attain a favorable prognosis with a comprehensive treatment program based on surgical treatment. However, the current treatment options for advanced thyroid cancer are still limited. In recent years, chimeric antigen receptor-modified T-cell (CAR-T) therapy has received widespread attention in the field of oncology treatment. It has achieved remarkable results in the treatment of hematologic tumors. However, due to the constraints of multiple factors, the therapeutic efficacy of CAR-T therapy for solid tumors, including thyroid cancer, has not yet met expectations. This review outlines the fundamental structure and treatment strategies of CAR-T cells, provides an overview of the advancements in both preclinical investigations and clinical trials focusing on targets associated with CAR-T cell therapy in treating thyroid cancer, and discusses the challenges and solutions to CAR-T cell therapy for thyroid cancer. In conclusion, CAR-T cell therapy is a promising therapeutic approach for thyroid cancer, and we hope that our review will provide a timely and updated study of CAR-T cell therapy for thyroid cancer to advance the field. [ABSTRACT FROM AUTHOR]

Exosomes carry proteins, metabolites, nucleic acids and lipids fromtheir parent cell of origin. They are derived from cells through exocytosis, are ingested by target cells, and can transfer biological signals between local or distant cells. Therefore, exosomes are often modified in reaction to pathological processes, including infection, cancer, cardiovascular diseases and in response to metabolic perturbations such as obesity and diabetes, all of which involve a significant inflammatory aspect. Here, we discuss how immune cell-derived exosomes origin from neutrophils, T lymphocytes, macrophages impact on the immune reprogramming of diabetes and the associated complications. Besides, exosomes derived from stem cells and their immunomodulatory properties and anti-inflammation effect in diabetes are also reviewed. Moreover, As an important addition to previous reviews, we describes promising directions involving engineered exosomes as well as current challenges of clinical applications in diabetic therapy. Further research on exosomes will explore their potential in translational medicine and provide new avenues for the development of effective clinical diagnostics and therapeutic strategies for immunoregulation of diabetes. [ABSTRACT FROM AUTHOR]

Abdominal aortic aneurysm (AAA) is characterized by inflammatory cell infiltration, extracellular matrix (ECM) degradation, and vascular smooth muscle cell (SMC) dysfunction. The inflammatory cells involved in AAA mainly include immune cells including macrophages, neutrophils, T-lymphocytes and B lymphocytes and endothelial cells. As the blood vessel wall expands, more and more lymphocytes infiltrate into the outer membrane. It was found that more than 50% of lymphocytes in AAA tissues were CD3+ T cells, including CD4+, CD8+T cells, gd T cells and regulatory T cells (Tregs). Due to the important role of T cells in inflammatory response, an increasing number of researchers have paid attention to the role of T cells in AAA and dug into the relevant mechanism. Therefore, this paper focuses on reviewing the immunoregulatory role of T cells in AAA and their role in immunotherapy, seeking potential targets for immunotherapy and putting forward future research directions. [ABSTRACT FROM AUTHOR]

Cyclic guanosine monophosphate-adenosine monophosphate (cGAMP) synthase (cGAS) detects infections or tissue damage by binding to microbial or self-DNA in the cytoplasm. Upon binding DNA, cGAS produces cGAMP that binds to and activates the adaptor protein stimulator of interferon genes (STING), which then activates the kinases IKK and TBK1 to induce the secretion of interferons and other cytokines. Recently, a series of studies demonstrated that the cGAS-STING pathway, a vital component of host innate immunity, might play an important role in anticancer immunity, though its mechanism remains to be elucidated. In this review, we highlight the latest understanding of the cGAS-STING pathway in tumor development and the advances in combination therapy of STING agonists and immunotherapy. [ABSTRACT FROM AUTHOR]

Liver fibrosis is a global health problem caused by chronic liver injury resulting from various factors. Hepatic stellate cells (HSCs) have been found to play a major role in liver fibrosis, and pathological stimuli lead to their transdifferentiation into myofibroblasts. Complex multidirectional interactions between HSCs, immune cells, and cytokines are also critical for the progression of liver fibrosis. Despite the advances in treatments for liver fibrosis, they do not meet the current medical needs. Exosomes are extracellular vesicles of 30-150 nm in diameter and are capable of intercellular transport of molecules such as lipids, proteins and nucleic acids. As an essential mediator of intercellular communication, exosomes are involved in the physiological and pathological processes of many diseases. In liver fibrosis, exosomes are involved in the pathogenesis mainly by regulating the activation of HSCs and the interaction between HSCs and immune cells. Serum-derived exosomes are promising biomarkers of liver fibrosis. Exosomes also have promising therapeutic potential in liver fibrosis. Exosomes derived from mesenchymal stem cells and other cells exhibit anti-liver fibrosis effects. Moreover, exosomes may serve as potential therapeutic targets for liver fibrosis and hold promise in becoming drug carriers for liver fibrosis treatment. [ABSTRACT FROM AUTHOR]

Lung cancer is the leading cause of cancer-related deaths worldwide, and insights into its underlying mechanisms as well as potential therapeutic strategies are urgently needed. The microbiome plays an important role in human health, and is also responsible for the initiation and progression of lung cancer through its induction of inflammatory responses and participation in immune regulation, as well as for its role in the generation of metabolic disorders and genotoxicity. Here, the distribution of human microflora along with its biological functions, the relationship between the microbiome and clinical characteristics, and the role of the microbiome in clinical treatment of lung cancer were comprehensively reviewed. This review provides a basis for the current understanding of lung cancer mechanisms with a focus on the microbiome, and contributes to future decisions on treatment management. [ABSTRACT FROM AUTHOR]

Neutralizing antibodies (NAbs) are central players in the humoral immunity that defends the body from SARS-CoV-2 infection by blocking viral entry into host cells and neutralizing their biological effects. Even though NAbs primarily work by neutralizing viral antigens, on some occasions, they may also combat the SARSCoV-2 virus escaping neutralization by employing several effector mechanisms in collaboration with immune cells like natural killer (NK) cells and phagocytes. Besides their prophylactic and therapeutic roles, antibodies can be used for COVID-19 diagnosis, severity evaluation, and prognosis assessment in clinical practice. Furthermore, the measurement of NAbs could have key implications in determining individual or herd immunity against SARS-CoV-2, vaccine effectiveness, and duration of the humoral protective response, as well as aiding in the selection of suitable individuals who can donate convalescent plasma to treat infected people. Despite all these clinical applications of NAbs, using them in clinical settings can present some challenges. This review discusses the protective functions, possible protective mechanisms against SARS-CoV-2, and potential clinical applications of NAbs in COVID-19. This article also highlights the possible challenges and solutions associated with COVID-19 antibody-based prophylaxis, therapy, and vaccination. [ABSTRACT FROM AUTHOR]

Neutralizing antibodies (NAbs) are central players in the humoral immunity that defends the body from SARS-CoV-2 infection by blocking viral entry into host cells and neutralizing their biological effects. Even though NAbs primarily work by neutralizing viral antigens, on some occasions, they may also combat the SARS-CoV-2 virus escaping neutralization by employing several effector mechanisms in collaboration with immune cells like natural killer (NK) cells and phagocytes. Besides their prophylactic and therapeutic roles, antibodies can be used for COVID-19 diagnosis, severity evaluation, and prognosis assessment in clinical practice. Furthermore, the measurement of NAbs could have key implications in determining individual or herd immunity against SARS-CoV-2, vaccine effectiveness, and duration of the humoral protective response, as well as aiding in the selection of suitable individuals who can donate convalescent plasma to treat infected people. Despite all these clinical applications of NAbs, using them in clinical settings can present some challenges. This review discusses the protective functions, possible protective mechanisms against SARS-CoV-2, and potential clinical applications of NAbs in COVID-19. This article also highlights the possible challenges and solutions associated with COVID-19 antibody-based prophylaxis, therapy, and vaccination.

With the arrival of the era of tumor immunotherapy, Immune Checkpoint Inhibitors have benefited countless tumor patients. However, the emergence of Immune-Related Adverse Events, especially Immune Checkpoint Inhibitor-Mediated Colitis (IMC), has become an important obstacle to immunotherapy. Therefore, it is very important to clarify themechanism and influencing factors of IMC. The effect of gut microbiota on IMC is gradually becoming a research hotspot. Gut microbiota from different phyla can affect IMC by regulating innate and acquired immunity of tumor patients in various ways. In this review, wemake a systematic and comprehensive introduction of the effect of gut microbiota on IMC. Through understanding the specific effects of gut microbiota on IMC, and then exploring the possibility of reducing IMC by regulating gut microbiota. [ABSTRACT FROM AUTHOR]

Programmed cell death protein-1 (PD-1) is a checkpoint receptor expressed on the surface of various immune cells. PD-L1, the natural receptor for PD-1, is mainly expressed in tumor cells. Studies have indicated that PD-1 and PD-L1 are closely associated with the progression of human cancers and are promising biomarkers for cancer therapy. Moreover, the interaction of PD-1 and PD-L1 is one of the important mechanism by which human tumors generate immune escape. This article provides a review on the role of PDL1/PD-1, mechanisms of immune response and resistance, as well as immunerelated adverse events in the treatment of anti-PD-1/PD-L1 immunotherapy in human cancers. Moreover, we summarized a large number of clinical trials to successfully reveal that PD-1/PD-L1 Immune-checkpoint inhibitors have manifested promising therapeutic effects, which have been evaluated from different perspectives, including overall survival, objective effective rate and medium progression-free survival. Finally, we pointed out the current problems faced by PD-1/PD-L1 Immune-checkpoint inhibitors and its future prospects. Although PD-1/PD-L1 immune checkpoint inhibitors have been widely used in the treatment of human cancers, tough challenges still remain. Combination therapy and predictive models based on integrated biomarker determination theory may be the future directions for the application of PD-1/PD-L1 Immune-checkpoint inhibitors in treating human cancers. [ABSTRACT FROM AUTHOR]

Mast cells (MCs) are bone-marrow-derived haematopoietic cells that are widely distributed in human tissues. When activated, they will release tryptase, histamine and other mediators that play major roles in a diverse array of diseases/disorders, including allergies, inflammation, cardiovascular diseases, autoimmune diseases, cancers and even death. The multiple pathological effects of MCs have made their stabilizers a research hotspot for the treatment of related diseases. To date, the clinically available MC stabilizers are limited. Considering the rapidly increasing incidence rate and widespread prevalence of MC-related diseases, a comprehensive reference is needed for the clinicians or researchers to identify and choose efficacious MC stabilizers. This review analyzes the mechanism of MC activation, and summarizes the progress made so far in the development of MC stabilizers. MC stabilizers are classified by the action mechanism here, including acting on cell surface receptors, disturbing signal transduction pathways and interfering exocytosis systems. Particular emphasis is placed on the clinical applications and the future development direction of MC stabilizers., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Cao and Gao.)

Programmed cell death protein-1 (PD-1) is a checkpoint receptor expressed on the surface of various immune cells. PD-L1, the natural receptor for PD-1, is mainly expressed in tumor cells. Studies have indicated that PD-1 and PD-L1 are closely associated with the progression of human cancers and are promising biomarkers for cancer therapy. Moreover, the interaction of PD-1 and PD-L1 is one of the important mechanism by which human tumors generate immune escape. This article provides a review on the role of PD-L1/PD-1, mechanisms of immune response and resistance, as well as immune-related adverse events in the treatment of anti-PD-1/PD-L1 immunotherapy in human cancers. Moreover, we summarized a large number of clinical trials to successfully reveal that PD-1/PD-L1 Immune-checkpoint inhibitors have manifested promising therapeutic effects, which have been evaluated from different perspectives, including overall survival, objective effective rate and medium progression-free survival. Finally, we pointed out the current problems faced by PD-1/PD-L1 Immune-checkpoint inhibitors and its future prospects. Although PD-1/PD-L1 immune checkpoint inhibitors have been widely used in the treatment of human cancers, tough challenges still remain. Combination therapy and predictive models based on integrated biomarker determination theory may be the future directions for the application of PD-1/PD-L1 Immune-checkpoint inhibitors in treating human cancers.

Metastatic dissemination represents a hallmark of cancer that is responsible for the high mortality rate. Recently, emerging evidence demonstrates a time-series event—pre-metastatic niche (PMN) has a profound impact on cancer metastasis. Exosomes, cell-free DNA (cfDNA), circulating tumor cells (CTC), and tumor microenvironment components, as critical components in PMN establishment, could be monitored by liquid biopsy. Intensive studies based on the molecular profile of liquid biopsy have made it a viable alternative to tissue biopsy. Meanwhile, the complex molecular mechanism and intercellular interaction are great challenges for applying liquid biopsy in clinical practice. This article reviews the cellular and molecular components involved in the establishment of the PMN and the promotion of metastasis, as well as the mechanisms of their interactions. Better knowledge of the characteristics of the PMN may facilitate the application of liquid biopsy for clinical diagnosis, prognosis, and treatment. [ABSTRACT FROM AUTHOR]

Combination antiretroviral therapy (cART) effectively blocks HIV replication but cannot completely eliminate HIV from the body mainly due to establishment of a viral reservoir. To date, clinical strategies designed to replace cART for life and alternatively to eliminate the HIV reservoir have failed. The reduced expression of viral antigens in the latently infected cells is one of the main reasons behind the failure of the strategies to purge the HIV reservoir. This situation has forced the scientific community to search alternative therapeutic strategies to control HIV infection. In this regard, recent findings have pointed out extracellular vesicles as therapeutic agents with enormous potential to control HIV infection. This review focuses on their role as pro-viral and anti-viral factors, as well as their potential therapeutic applications. [ABSTRACT FROM AUTHOR]

Combination antiretroviral therapy (cART) effectively blocks HIV replication but cannot completely eliminate HIV from the body mainly due to establishment of a viral reservoir. To date, clinical strategies designed to replace cART for life and alternatively to eliminate the HIV reservoir have failed. The reduced expression of viral antigens in the latently infected cells is one of the main reasons behind the failure of the strategies to purge the HIV reservoir. This situation has forced the scientific community to search alternative therapeutic strategies to control HIV infection. In this regard, recent findings have pointed out extracellular vesicles as therapeutic agents with enormous potential to control HIV infection. This review focuses on their role as pro-viral and anti-viral factors, as well as their potential therapeutic applications.

Currently, immunotherapy is being widely used for treating cancers. However, the significant heterogeneity in patient responses is a major challenge for its successful application. CD8-positive T cells (CD8 + T cells) play a critical role in immunotherapy. Both their infiltration and functional status in tumors contribute to treatment outcomes. Therefore, accurate monitoring of CD8 + T cells, a potential biomarker, may improve therapeutic strategy. Positron emission tomography (PET) is an optimal option which can provide molecular imaging with enhanced specificity. This review summarizes the mechanism of action of CD8 + T cells in immunotherapy, and highlights the recent advancements in PET-based tracers that can visualize CD8 + T cells and discusses their clinical applications to elucidate their potential role in cancer immunotherapy., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Zhang, Du, Wang, Cui, Wang, Zhao, Li and Li.)

The majority of patients with thyroid cancer can attain a favorable prognosis with a comprehensive treatment program based on surgical treatment. However, the current treatment options for advanced thyroid cancer are still limited. In recent years, chimeric antigen receptor-modified T-cell (CAR-T) therapy has received widespread attention in the field of oncology treatment. It has achieved remarkable results in the treatment of hematologic tumors. However, due to the constraints of multiple factors, the therapeutic efficacy of CAR-T therapy for solid tumors, including thyroid cancer, has not yet met expectations. This review outlines the fundamental structure and treatment strategies of CAR-T cells, provides an overview of the advancements in both preclinical investigations and clinical trials focusing on targets associated with CAR-T cell therapy in treating thyroid cancer, and discusses the challenges and solutions to CAR-T cell therapy for thyroid cancer. In conclusion, CAR-T cell therapy is a promising therapeutic approach for thyroid cancer, and we hope that our review will provide a timely and updated study of CAR-T cell therapy for thyroid cancer to advance the field., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Sun, Wang, Zhao and Ling.)

CD44 is a ubiquitous leukocyte adhesion molecule involved in cell-cell interaction, cell adhesion, migration, homing and differentiation. CD44 can mediate the interaction between leukemic stem cells and the surrounding extracellular matrix, thereby inducing a cascade of signaling pathways to regulate their various behaviors. In this review, we focus on the impact of CD44s/CD44v as biomarkers in leukemia development and discuss the current research and prospects for CD44-related interventions in clinical application., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Wu, Tan, Li, Han, Zhang and Lin.)

Exosomes carry proteins, metabolites, nucleic acids and lipids from their parent cell of origin. They are derived from cells through exocytosis, are ingested by target cells, and can transfer biological signals between local or distant cells. Therefore, exosomes are often modified in reaction to pathological processes, including infection, cancer, cardiovascular diseases and in response to metabolic perturbations such as obesity and diabetes, all of which involve a significant inflammatory aspect. Here, we discuss how immune cell-derived exosomes origin from neutrophils, T lymphocytes, macrophages impact on the immune reprogramming of diabetes and the associated complications. Besides, exosomes derived from stem cells and their immunomodulatory properties and anti-inflammation effect in diabetes are also reviewed. Moreover, As an important addition to previous reviews, we describes promising directions involving engineered exosomes as well as current challenges of clinical applications in diabetic therapy. Further research on exosomes will explore their potential in translational medicine and provide new avenues for the development of effective clinical diagnostics and therapeutic strategies for immunoregulation of diabetes., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. The reviewer J-HC declared a shared parent affiliation with the authors NL, YY, ZX, DC, and YG to the handling editor at the time of review., (Copyright © 2024 Li, Hu, Li, Ye, Bao, Xu, Chen, Tang and Gu.)

Abdominal aortic aneurysm (AAA) is characterized by inflammatory cell infiltration, extracellular matrix (ECM) degradation, and vascular smooth muscle cell (SMC) dysfunction. The inflammatory cells involved in AAA mainly include immune cells including macrophages, neutrophils, T-lymphocytes and B lymphocytes and endothelial cells. As the blood vessel wall expands, more and more lymphocytes infiltrate into the outer membrane. It was found that more than 50% of lymphocytes in AAA tissues were CD3 + T cells, including CD4 + , CD8 + T cells, γδ T cells and regulatory T cells (Tregs). Due to the important role of T cells in inflammatory response, an increasing number of researchers have paid attention to the role of T cells in AAA and dug into the relevant mechanism. Therefore, this paper focuses on reviewing the immunoregulatory role of T cells in AAA and their role in immunotherapy, seeking potential targets for immunotherapy and putting forward future research directions., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Gong, Tian and Li.)

Cyclic guanosine monophosphate-adenosine monophosphate (cGAMP) synthase (cGAS) detects infections or tissue damage by binding to microbial or self-DNA in the cytoplasm. Upon binding DNA, cGAS produces cGAMP that binds to and activates the adaptor protein stimulator of interferon genes (STING), which then activates the kinases IKK and TBK1 to induce the secretion of interferons and other cytokines. Recently, a series of studies demonstrated that the cGAS-STING pathway, a vital component of host innate immunity, might play an important role in anticancer immunity, though its mechanism remains to be elucidated. In this review, we highlight the latest understanding of the cGAS-STING pathway in tumor development and the advances in combination therapy of STING agonists and immunotherapy., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Chen, Liu, Jiang, Meng and Wei.)

Liver fibrosis is a global health problem caused by chronic liver injury resulting from various factors. Hepatic stellate cells (HSCs) have been found to play a major role in liver fibrosis, and pathological stimuli lead to their transdifferentiation into myofibroblasts. Complex multidirectional interactions between HSCs, immune cells, and cytokines are also critical for the progression of liver fibrosis. Despite the advances in treatments for liver fibrosis, they do not meet the current medical needs. Exosomes are extracellular vesicles of 30-150 nm in diameter and are capable of intercellular transport of molecules such as lipids, proteins and nucleic acids. As an essential mediator of intercellular communication, exosomes are involved in the physiological and pathological processes of many diseases. In liver fibrosis, exosomes are involved in the pathogenesis mainly by regulating the activation of HSCs and the interaction between HSCs and immune cells. Serum-derived exosomes are promising biomarkers of liver fibrosis. Exosomes also have promising therapeutic potential in liver fibrosis. Exosomes derived from mesenchymal stem cells and other cells exhibit anti-liver fibrosis effects. Moreover, exosomes may serve as potential therapeutic targets for liver fibrosis and hold promise in becoming drug carriers for liver fibrosis treatment., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Liu, Zheng, Yang, Liu, Wu, Gao and Zhang.)

Natural killer (NK) cells are innate lymphoid cells that hold tremendous potential for effective immunotherapy for a broad range of cancers. Due to the mode of NK cell killing requiring one–to-one target engagement and site directed release of cytolytic granules, the therapeutic potential of NK cells has been most extensively explored in hematological malignancies. However, their ability to precisely kill antibody coated cells, cancer stem cells (CSCs) and genotoxically altered cells, while maintaining tolerance to healthy cells makes them appealing therapeutic effectors for all cancer forms, including metastases. Due to their release of pro-inflammatory cytokines, NK cells may potently reverse the anti-inflammatory tumor microenvironment (TME) and augment adaptive immune responses by promoting differentiation, activation and/ or recruitment of accessory immune cells to sites of malignancy. Nevertheless, integrated and coordinated mechanisms of subversion of NK cell activity against the tumor and its microenvironment exist. Although our understanding of the receptor ligand interactions that regulate NK cell functionality has evolved remarkably, the diversity of ligands and receptors is complex, as is their mechanistic foundations in regulating NK cell function. In this article, we review the literature and highlight how the TME manipulates the NK cell phenotypes, genotypes and tropism to evade tumor recognition and elimination. We discuss counter strategies that may be adopted to augment the efficacy of NK cell anti-tumor surveillance, the clinical trials that have been undertaken so far in solid malignancies, critically weighing the challenges and opportunities with this approach.

The research in extracellular vesicles (EVs) has been rising during the last decade. However, there is no clear consensus on the most accurate protocol to isolate and analyze them. Besides, most of the current protocols are difficult to implement in a hospital setting due to being very time consuming or to requirements of specific infrastructure. Thus, our aim is to compare five different protocols (comprising two different medium-speed differential centrifugation protocols; commercially polymeric precipitation -exoquick-; acid precipitation; and ultracentrifugation) for blood and urine samples to determine the most suitable one for the isolation of EVs. Nanoparticle tracking analysis, flow cytometry, western blot, electronic microscopy and spectrophotometry were used to characterize basic aspects of EVs such us concentration, size distribution, cell-origin and transmembrane markers and RNA concentration. The highest EV concentrations were obtained using the exoquick protocol, followed by both differential centrifugation protocols, while the ultracentrifugation and acid-precipitation protocols yielded considerably lower EV concentrations. The five protocols isolated EVs of similar characteristics regarding markers and RNA concentration however standard protocol recovered only small EVs. EV isolated with exoquick presented difficult to be analyzed with western blot. The RNA concentrations obtained from urine-derived EVs were similar to those obtained from blood-derived ones, despite the urine EV concentration being 10 to 20 times lower. We consider that a medium-speed differential centrifugation could be suitable to be applied in a hospital setting due to require the simplest infrastructure and recover higher concentration of EV than standard protocol. A workflow from sampling to characterization of EVs is proposed.

Lung cancer is the leading cause of cancer-related deaths worldwide, and insights into its underlying mechanisms as well as potential therapeutic strategies are urgently needed. The microbiome plays an important role in human health, and is also responsible for the initiation and progression of lung cancer through its induction of inflammatory responses and participation in immune regulation, as well as for its role in the generation of metabolic disorders and genotoxicity. Here, the distribution of human microflora along with its biological functions, the relationship between the microbiome and clinical characteristics, and the role of the microbiome in clinical treatment of lung cancer were comprehensively reviewed. This review provides a basis for the current understanding of lung cancer mechanisms with a focus on the microbiome, and contributes to future decisions on treatment management., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Sun, Wen, Liu, Wang, Jing, Gu, Jiang and Wang.)

Natural killer (NK) cells are innate lymphoid cells that hold tremendous potential for effective immunotherapy for a broad range of cancers. Due to the mode of NK cell killing, requiring one-to-one target engagement and site-directed release of cytolytic granules, the therapeutic potential of NK cells has been most extensively explored in hematological malignancies. However, their ability to precisely kill antibody coated cells, cancer stem cells, and genotoxically altered cells, while maintaining tolerance to healthy cells makes them appealing therapeutic effectors for all cancer forms, including metastases. Due to their release of pro-inflammatory cytokines, NK cells may potently reverse the antiinflammatory tumor microenvironment (TME) and augment adaptive immune responses by promoting differentiation, activation, and/or recruitment of accessory immune cells to sites of malignancy. Nevertheless, integrated and coordinated mechanisms of subversion of NK cell activity against the tumor and its microenvironment exist. Although our understanding of the receptor ligand interactions that regulate NK cell functionality has evolved remarkably, the diversity of ligands and receptors is complex, as is their mechanistic foundations in regulating NK cell function. In this article, we review the literature and highlight how the TME manipulates the NK cell phenotypes, genotypes, and tropism to evade tumor recognition and elimination. We discuss counter strategies that may be adopted to augment the efficacy of NK cell anti-tumor surveillance, the clinical trials that have been undertaken so far in solid malignancies, critically weighing the challenges and opportunities with this approach. [ABSTRACT FROM AUTHOR]

The research in extracellular vesicles (EVs) has been rising during the last decade. However, there is no clear consensus on the most accurate protocol to isolate and analyze them. Besides, most of the current protocols are difficult to implement in a hospital setting due to being very time-consuming or to requirements of specific infrastructure.Thus, our aim is to compare five different protocols (comprising two different medium-speed differential centrifugation protocols; commercially polymeric precipitation - exoquick - acid precipitation; and ultracentrifugation) for blood and urine samples to determine the most suitable one for the isolation of EVs. Nanoparticle tracking analysis, flow cytometry, western blot (WB), electronic microscopy, and spectrophotometry were used to characterize basic aspects of EVs such as concentration, size distribution, cell-origin and transmembrane markers, and RNA concentration. The highest EV concentrations were obtained using the exoquick protocol, followed by both differential centrifugation protocols, while the ultracentrifugation and acid-precipitation protocols yielded considerably lower EV concentrations.The five protocols isolated EVs of similar characteristics regarding markers and RNA concentration; however, standard protocol recovered only small EVs. EV isolated with exoquick presented difficult to be analyzed withWB.The RNA concentrations obtained from urine-derived EVs were similar to those obtained from blood-derived ones, despite the urine EV concentration being 10-20 times lower.We consider that a medium-speed differential centrifugation could be suitable to be applied in a hospital setting as it requires the simplest infrastructure and recovers higher concentration of EV than standard protocol. A workflow from sampling to characterization of EVs is proposed. [ABSTRACT FROM AUTHOR]

With the arrival of the era of tumor immunotherapy, Immune Checkpoint Inhibitors have benefited countless tumor patients. However, the emergence of Immune-Related Adverse Events, especially Immune Checkpoint Inhibitor-Mediated Colitis (IMC), has become an important obstacle to immunotherapy. Therefore, it is very important to clarify the mechanism and influencing factors of IMC. The effect of gut microbiota on IMC is gradually becoming a research hotspot. Gut microbiota from different phyla can affect IMC by regulating innate and acquired immunity of tumor patients in various ways. In this review, we make a systematic and comprehensive introduction of the effect of gut microbiota on IMC. Through understanding the specific effects of gut microbiota on IMC, and then exploring the possibility of reducing IMC by regulating gut microbiota., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Han, Zang, Liu and Chen.)

Programmed cell death protein-1 (PD-1) is a checkpoint receptor expressed on the surface of various immune cells. PD-L1, the natural receptor for PD-1, is mainly expressed in tumor cells. Studies have indicated that PD-1 and PD-L1 are closely associated with the progression of human cancers and are promising biomarkers for cancer therapy. Moreover, the interaction of PD-1 and PD-L1 is one of the important mechanism by which human tumors generate immune escape. This article provides a review on the role of PD-L1/PD-1, mechanisms of immune response and resistance, as well as immune-related adverse events in the treatment of anti-PD-1/PD-L1 immunotherapy in human cancers. Moreover, we summarized a large number of clinical trials to successfully reveal that PD-1/PD-L1 Immune-checkpoint inhibitors have manifested promising therapeutic effects, which have been evaluated from different perspectives, including overall survival, objective effective rate and medium progression-free survival. Finally, we pointed out the current problems faced by PD-1/PD-L1 Immune-checkpoint inhibitors and its future prospects. Although PD-1/PD-L1 immune checkpoint inhibitors have been widely used in the treatment of human cancers, tough challenges still remain. Combination therapy and predictive models based on integrated biomarker determination theory may be the future directions for the application of PD-1/PD-L1 Immune-checkpoint inhibitors in treating human cancers., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Tang, Chen, Li, Long, Shi, Yu, Wu, Han and Wang.)

Metastatic dissemination represents a hallmark of cancer that is responsible for the high mortality rate. Recently, emerging evidence demonstrates a time-series event-pre-metastatic niche (PMN) has a profound impact on cancer metastasis. Exosomes, cell-free DNA (cfDNA), circulating tumor cells (CTC), and tumor microenvironment components, as critical components in PMN establishment, could be monitored by liquid biopsy. Intensive studies based on the molecular profile of liquid biopsy have made it a viable alternative to tissue biopsy. Meanwhile, the complex molecular mechanism and intercellular interaction are great challenges for applying liquid biopsy in clinical practice. This article reviews the cellular and molecular components involved in the establishment of the PMN and the promotion of metastasis, as well as the mechanisms of their interactions. Better knowledge of the characteristics of the PMN may facilitate the application of liquid biopsy for clinical diagnosis, prognosis, and treatment., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Liu, Kong, Dang, Weng, Zheng, Ren, Lv, Li, Han and Han.)

An introduction is presented in which the editor discusses various reports within the issue on topics including the use of extracellular vesicles (EVs) as a liquid biopsy, urine-derived EV as a biomarker of kidney diseases, and five different EV isolation protocols.

Natural killer (NK) cells are innate lymphoid cells that hold tremendous potential for effective immunotherapy for a broad range of cancers. Due to the mode of NK cell killing, requiring one-to-one target engagement and site-directed release of cytolytic granules, the therapeutic potential of NK cells has been most extensively explored in hematological malignancies. However, their ability to precisely kill antibody coated cells, cancer stem cells, and genotoxically altered cells, while maintaining tolerance to healthy cells makes them appealing therapeutic effectors for all cancer forms, including metastases. Due to their release of pro-inflammatory cytokines, NK cells may potently reverse the anti-inflammatory tumor microenvironment (TME) and augment adaptive immune responses by promoting differentiation, activation, and/or recruitment of accessory immune cells to sites of malignancy. Nevertheless, integrated and coordinated mechanisms of subversion of NK cell activity against the tumor and its microenvironment exist. Although our understanding of the receptor ligand interactions that regulate NK cell functionality has evolved remarkably, the diversity of ligands and receptors is complex, as is their mechanistic foundations in regulating NK cell function. In this article, we review the literature and highlight how the TME manipulates the NK cell phenotypes, genotypes, and tropism to evade tumor recognition and elimination. We discuss counter strategies that may be adopted to augment the efficacy of NK cell anti-tumor surveillance, the clinical trials that have been undertaken so far in solid malignancies, critically weighing the challenges and opportunities with this approach.

The research in extracellular vesicles (EVs) has been rising during the last decade. However, there is no clear consensus on the most accurate protocol to isolate and analyze them. Besides, most of the current protocols are difficult to implement in a hospital setting due to being very time-consuming or to requirements of specific infrastructure. Thus, our aim is to compare five different protocols (comprising two different medium-speed differential centrifugation protocols; commercially polymeric precipitation - exoquick - acid precipitation; and ultracentrifugation) for blood and urine samples to determine the most suitable one for the isolation of EVs. Nanoparticle tracking analysis, flow cytometry, western blot (WB), electronic microscopy, and spectrophotometry were used to characterize basic aspects of EVs such as concentration, size distribution, cell-origin and transmembrane markers, and RNA concentration. The highest EV concentrations were obtained using the exoquick protocol, followed by both differential centrifugation protocols, while the ultracentrifugation and acid-precipitation protocols yielded considerably lower EV concentrations. The five protocols isolated EVs of similar characteristics regarding markers and RNA concentration; however, standard protocol recovered only small EVs. EV isolated with exoquick presented difficult to be analyzed with WB. The RNA concentrations obtained from urine-derived EVs were similar to those obtained from blood-derived ones, despite the urine EV concentration being 10-20 times lower. We consider that a medium-speed differential centrifugation could be suitable to be applied in a hospital setting as it requires the simplest infrastructure and recovers higher concentration of EV than standard protocol. A workflow from sampling to characterization of EVs is proposed.