Gut Microbiome as a Potential Factor for Modulating Resistance to Cancer Immunotherapy.

Gut microbiota refers to the diverse community of more than 100 trillion microorganisms residing in our intestines. It is now known that any shift in the composition of gut microbiota from that present during the healthy state in an individual is associated with predisposition to multiple pathological conditions, such as diabetes, autoimmunity, and even cancer. Currently, therapies targeting programmed cell death protein 1/programmed cell death 1 ligand 1 or cytotoxic T-lymphocyte antigen-4 are the focus of cancer immunotherapy and are widely applied in clinical treatment of various tumors. Owing to relatively low overall response rate, however, it has been an ongoing research endeavor to identify the mechanisms or factors for improving the therapeutic efficacy of these immunotherapies. Other than causing mutations that affect gene expression, some gut bacteria may also activate or repress the host's response to immune checkpoint inhibitors. In this review, we have described recent advancements made in understanding the regulatory relationship between gut microbiome and cancer immunotherapy. We have also summarized the potential molecular mechanisms behind this interaction, which can serve as a basis for utilizing different kinds of gut bacteria as promising tools for reversing immunotherapy resistance in cancer.

Shui L ，Yang X ，Li J ，Yi C ，Sun Q ，Zhu H ... -  《Frontiers in Immunology》

Exploring the Emerging Role of the Gut Microbiota and Tumor Microenvironment in Cancer Immunotherapy.

The tumor microenvironment (TME) is a complex ecosystem, which includes many different types of cells, abnormal vascular systems, and immunosuppressive cytokines. TME serves an important function in tumor tolerance and escapes from immune surveillance leading to tumor progression. Indeed, there is increasing evidence that gut microbiome is associated with cancer in a variety of ways, as specific microbial signatures are known to promote cancer development and influence safety, tolerability, and efficacy of therapies. Studies over the past five years have shown that the composition of the intestinal microbiota has a significant impact on the efficacy of anticancer immunosurveillance, which contribute to the therapeutic activity of cancer immunotherapies based on targeting cytotoxic T lymphocyte protein 4 (CTLA-4) or programmed cell death protein 1 (PD-1)-programmed cell death 1 ligand 1 (PD-L1) axis. In this review, we mainly discuss the impact of TME on cancer and immunotherapy through immune-related mechanisms. We subsequently discuss the influence of gut microbiota and its metabolites on the host immune system and the formation of TME. In addition, this review also summarizes the latest research on the role of gut microbiota in cancer immunotherapy.

Qiu Q ，Lin Y ，Ma Y ，Li X ，Liang J ，Chen Z ，Liu K ，Huang Y ，Luo H ，Huang R ，Luo L ... -  《Frontiers in Immunology》

Potential mechanisms and targeting strategies of the gut microbiota in antitumor immunity and immunotherapy.

Immunotherapies, notably immune checkpoints inhibitors that target programmed death 1/programmed death ligand 1(PD-1/PD-L1) and cytotoxic T lymphocyte-associated antigen 4 (CTLA-4), had profoundly changed the way advanced and metastatic cancers are treated and dramatically improved overall and progression-free survival. This review article aimed to explore the underlying molecular mechanisms by which the gut microbiota affects antitumor immunity and the efficacy of cancer immunotherapy. We summarized the latest knowledge supporting the associations among the gut microbiota, antitumor immunity, and immunotherapy. Moreover, we disscussed the therapeutic strategy for improving immunotherapy efficacy by modulating gut microbiota in cancer treatment. The potential molecular mechanisms underlying these associations are explained in terms of four aspects: immunomodulation, molecular mimicry, mamps, and microbial metabolites. The gut microbiota significantly impacts antitumor immunity and alters the effectiveness of cancer immunotherapy.

Yin Q ，Ni JJ ，Ying JE 《Immunity Inflammation and Disease》

Manipulating Gut Microbiota Composition to Enhance the Therapeutic Effect of Cancer Immunotherapy.

Yi M ，Jiao D ，Qin S ，Chu Q ，Li A ，Wu K ... -  《-》

Gut microbiome in cancer immunotherapy: Current trends, translational challenges and future possibilities.

Gut microbiota is regarded as a crucial regulator of the immune system. Healthy gut microbiota plays a specialized role in host xenobiotics, nutrition, drug metabolism, regulation of the structural integrity of the gut mucosal barrier, defense against infections, and immunomodulation. It is now understood that any imbalance in gut microbiota composition from that present in a healthy state is linked to genetic susceptibility to a number of metabolic disorders, including diabetes, autoimmunity, and cancer. Recent research has suggested that immunotherapy can treat many different cancer types with fewer side effects and better ability to eradicate tumors than conventional chemotherapy or radiotherapy. However, a significant number of patients eventually develop immunotherapy resistance. A strong correlation was observed between the composition of the gut microbiome and the effectiveness of treatment by examining the variations between populations that responded to immunotherapy and those that did not. Therefore, we suggest that modulating the microbiome could be a potential adjuvant therapy for cancer immunotherapy and that the architecture of the gut microbiota may be helpful in explaining the variation in treatment response. Herein, we focus on recent research on the interactions among the gut microbiome, host immunity, and cancer immunotherapy. In addition, we highlighted the clinical manifestations, future opportunities, and limitations of microbiome manipulation in cancer immunotherapy.

Pandey P ，Khan F 《-》