In recent years, numerous studies have shown that gut microbiota can modulate antitumor response, as well as decrease the risk of colitis due to ICIs in patients receiving immunotherapy. The functional role of the microbiota in regulating not only mucosal but also systemic immune . Inulin is a prebioticthat is, a nondigestible substance that "feeds" healthy bacteria in the gut, thereby selectively . Growing evidence indicates that gut microbiota is not only involved in carcinogenesis but also has an impact on the efficacy and toxicity of cancer therapy. The composition of the gut microbiome influences the response of cancer patients to immunotherapies. The role of the gut microbiome in cancer is gradually coming into focus. Peng et al. For example, intestinal microorganisms play a key role in the effectiveness of programmed cell death 1 (PD1) and cytotoxic T lymphocyte-associated antigen 4 (CTLA4) blockade. Several other cancers, including nasopharyngeal carcinoma (NPC), have yet to be investigated. The intestines are the main location of the hundreds of millions of microbes that form the microbiota. Abstract The gastrointestinal tract (GIT) is the largest immune organ and maintains systemic immune homeostasis in the presence of bacterial challenge. His lab is pursuing an alternative approach by developing a colon-retentive gel made of inulina widely-consumed dietary fiberthat can modulate the gut microbiome to improve responses to cancer immunotherapy. ( 5) and Davar et al. Gut Microbiota in Cancer Immune Response and Immunotherapy Highlights Immunotherapy is a promising treatment for cancer, the responses to which might be affected by the gut microbiota. Notably, certain studies have demonstrated that the gut microbiota serves a key role in regulating a patient's response to immunotherapy. A review paper published in JAMA Oncology by investigators from Brigham and Women's Hospital captures the current understanding of the connection between the gut microbiome and therapeutic response. report first-in-human clinical trials to test whether fecal microbiota transplantation (FMT) can affect how metastatic melanoma patients respond to anti-PD-1 immunotherapy (see the Perspective by Woelk and Snyder). A growing body of research suggests that altering the gut microbiota can improve the efficacy of anticancer medicines. These include phage antigens that are cross-reactive with tumor cells, cell wall-derived muropeptides such as glutaminylmuramyl-dipeptide (GMDP), and commensal-derived inosine, all of which converge on increased type 1 . "The Potential of the Gut Microbiome to Reshape the Cancer Therapy Paradigm: A Review" JAMA Oncology DOI: 10.1001/jamaoncol.2022.0494, JAMA Oncology . Anticancer immune responses were studied not only for individual commensal bacterium species but also for a consortium of several bacteria. Immunotherapy is a promising treatment for cancer, the responses to which might be affected by the gut microbiota. Science, 350 (6264) (2015), pp. Gut . The Gut Microbiota in Response and Toxicity to Immunotherapy. This assignment has two parts. Background Immune checkpoint inhibitors (ICIs) are promising agents for unresectable hepatocellular carcinoma (uHCC), but lack effective biomarker to predict outcomes. these include the following: (1) effects on other microorganisms in the gut causing shifts in the ecosystem 51, (2) effects on the intestinal wall including enterocytes (with the induction of. The . . The present review analyzed recent progress of . The role of the gut microbiota in immune checkpoint blockade. in all three studies, faecal microbiota transplantation (fmt) to germ-free mice from individuals that responded to anti-pd1 therapy led to enhanced antitumour immunity compared with mice that. Immune elimination and immune escape are hallmarks of cancer, both of which can be partly bacteria dependent in shaping immunity by mediating host immunomodulation. The systemic anti-microbiota IgG repertoire can identify gut bacteria that translocate across gut barrier surfaces. anti-CTLA-4 and anti-PD-L1 antibody treatment, both in preclinical . Research on the interaction between the gut microbiome and immunity is an emerging field that examines the role of environmental factors, such as diet, as well as genetic and immune signals in metabolism, immunity, and host response to infection [].Studies on immune dysregulation may contribute to . Limeta A, Ji B, Levin M, Gatto F, Nielsen J. Meta-analysis of the gut microbiota in predicting response to cancer immunotherapy in metastatic melanoma. Gut microbiota affects the efficacy of immune checkpoint inhibitor-based immunotherapy. Certain gut microbes can help the immune system fight tumors and CCR scientists have figured out one way they do it. Gut microbiota has gained increasing attention due to its emerging role in regulating the immune system. Certain beneficial microbial species are known to have a range of effects on host antitumor immune responses, and cancer immunotherapy. Normal composition of gut microbiota, its diversity in number and type in different parts of the gut. The human gut microbiome modulates many host processes, including metabolism, inflammation, immune and intestinal epithelial cell responses. Cancer immunotherapy for solid tumors experienced a rebirth in the 2010s with the approval of checkpoint inhibitors (CPIs) that block . 2020;5:23. The gut microbiome has been implicated in many human pathologies. Study Design Go to The gastrointestinal tract (GIT) is the largest immune organ and maintains systemic immune homeostasis in the presence of bacterial challenge. The putative effects of commensal microbiota on cancer immunotherapy. 19 Indeed, a 'deviated' repertoire of . Circos plots illustrating the relationships of unique microbial taxa response to cancer immunotherapy agents (anti-CTLA-4 and/or . The gut is inhabited by diverse resident bacteria, of which, few enhance, while others inhibit the host response to immunotherapy. In one study, researchers from the University of Texas Southwestern Medical Center . Immune elimination and immune escape are hallmarks of cancer, both of which can be partly bacteria dependent in shaping immunity by mediating host immunomodulation. Microbiota enhance immunotherapy. "Overall, these findings support the potential of influencing the gut microbiota to diminish the side effects . The mechanisms involved in resistance to immunotherapy encompass tumor intrinsic factors and systemic factors including germline genetics and environmental factors (Science 2018;359:582-587, Appl Immunohistochem Mol Morphol 2018;26(2):e15-e21) with the effect of the gut microbiota on response to checkpoint blockade being detailed in a series of . We will review how patients' gut microbes modulate the benefit of cancer immunotherapy. The gut microbiome can modulate tumor response to immunotherapy, but its effect on HCC remains unclear. Both studies observed evidence of clinical . The intestinal microbiota can improve cancer immunotherapy and patient prognosis; therefore, manipulating the microbiota will become a new force to improve cancer immunotherapy. Furthermore, we consider the significance of gut microbiota as a potential biomarker for predicting the efficacy of cancer immunotherapy. Cancer immunotherapy is a very promising therapy by boosting the immune system to kill cancer cells and suppress tumor growth. JCI Insight. Although early studies primarily used murine models to assess these interactions, there is now . Here, we present our recent findings that specific gut-resident bacteria determine the immunotherapeutic responses associated with CTLA-4 checkpoint blockade. Adaptive Immune Response between the Host and the Gut Microbiota in Cancer The adaptive immune response is more specic to antigens, and is separate from the innate immune response, which can be affected by the gut microbiota in a benecial or harmful way. The GI microbiota and immune system interact in a complex network with the cancer cells through a TME modulation. Meta-analysis of the gut microbiota in predicting response to cancer immunotherapy in metastatic melanoma . A working knowledge of the microbiome is vital as we move forward in this age of precision medicine, and an understanding of the microbiome's influence on immune responses and cancer is key. Studies are increasingly investigating the association between the gut microbiota and the outcomes of immunotherapy in patients with cancer. Previous studies observed a mutual relationship between the gut microbiota and gastrointestinal immunity. Cancer is no exception, and distinct aspects of the microbiota have been reported to have either pro- or anti-tumor effects. Demonstrating its underlying mechanism could lead to new strategies to treat cancer. The breakdown of joint cartilage and bone as a result of a persistent immune response is one of the most common symptoms. Although the cause-effect relationship between gut microbiota and disease progression of cancer metastasis remains unclear, the dysbiosis induced by the gut microbiome mentioned above may promote the tumor-instigated inflammation and form potential tripartite interactions among the host immune system, the disseminated tumor, and the gut . Immune checkpoints have been aggressively investigated for anti-cancer immunotherapy. Microbiota can influence the response to cancer immunotherapy through multiple mechanisms. Bifidobacterium cocktail cooperates with immune checkpoint inhibitors (ICIs) blockade to promote and activate antitumor immunity. But the role of the microbiome goes beyond immunotherapy. The current known main mechanisms include: (1) Bacterial metabolites enter the circulation and bind to host cells through receptors, thus affecting the host immune system. When the gut microbiota is around to train the immune system, it is able to fine-tune responses to actual threats. In the present review, the potential associations between the gut microbiota, and cancer, host immunity and cancer . Two new studies, published February 1 in the Journal of Clinical Investigation, hint that a patient's immune cells may play a much more important role in the response to a type of immune checkpoint inhibitor than do tumor cells themselves.. Complex interplay between gut microbiota, immune system and cancer during immune-checkpoint inhibition. The Influence of Gut Microbiota on Tumor Immunity. investigated fecal microbiota signatures correlated with clinical response to anti-PD-1/PD-L1 immunotherapy in a cohort of patients with GI cancer (19 CRC, 23 GC, 14 esophageal carcinoma, and 18 other GI cancer types). Cancer can alter host immune response by activating immunosuppressive pathways; also, cancer may modulate gut microbiota. Methods From May 2018 to February 2020, patients receiving ICI treatment for uHCC were prospectively enrolled; their fecal . 16 - 18 In the last decade, major progress has been made in the comprehension of cancer development in interaction with the microbiota. A prime example is seen in immunotherapy, for which gut microbes determine the therapeutic responses associated with immune checkpoint inhibitors (ICIs) in preclinical models and patient cohorts. The mutualistic symbiosis between gut microbiota and host immunity raises the possibility that dysbiosis of the intestinal content also influences the outcome of cancer immunotherapy. Could microbial therapy boost cancer immunotherapy? Thus, the microbiome signature can predict clinical outcomes, prognosis, and immunotherapy responses. Immunotherapy efficacy and tolerability in cancer patients seem to be deeply affected by the gut microbiota and its metabolites ().The increasingly widespread use of ICIs has led to discovering new interactions between cancer treatment and the microbiome, depending on the crosstalk between three extremely complex, constantly evolving biological entities: microbiota, tumor, and immune system (). Microbiota . Science Translational Medicine , 2022; 14 (658) DOI: 10.1126/scitranslmed.abl3927 Given the role of the gut microbiota in modulating host immunity, it is fairly intuitive that it could significantly influence response and toxicity to various forms of cancer therapy. This review focuses on the correlation between intestinal microbiota and the outcome of tumor immunotherapy. At the same time, antibiotic exposure not only led to changes in the tumor immune microenvironment, but also altered the gut microbiota. More information: Liu L and Shah K, et al. Given the role of the gut microbiota in modulating immune response as detailed above, there is very little surprise that gut microbiota have been related to differences in treatment response to immunotherapeutic agents in various malignancies. Cancer immunotherapy, including immune checkpoint blockade (ICB), appears to have heterogeneous therapeutic effects in different individuals, partially attributed to the microbiota. Gut microbiota plays an important role in the occurrence and progress of tumors, and the immune system is also the dominant force in tumor control. The gut microbiota also appears to affect the response to immunotherapy. The human gut microbiome is a . Immune Cells May Be the Important Players in Immunotherapy Response. Anticancer immunotherapy, based on the administration of immune checkpoint inhibitory antibodies, blocks tumor growth as it is able to inhibit immunosuppressive pathways. The gut microbiota plays a critical part in the training and development of major components of the host innate and adaptive immune systems via direct sampling of gut bacteria for antigen . Studies have shown that the gut microbiota can regulate immune function to play an antitumor effect [ 23 - 29 ]. and Davar et al. Topic: Connection between the gut microbiota with cancer immune response/immunotherapy. The power of microbiota on the outcome of this immunotherapy has attracted much attention. Gut microbiome has been increasingly recognized for its influence on a diverse array of human diseases including cancer, and may also influence the outcome of cancer therapies. Direct Molecular and Cellular Interactions. It is also important to understand factors influencing the gut microbiome and strategies to manipulate the microbiome to augment therapeutic responses. This Special Issue invites original research and review articles which contribute to the understanding of the roles of . Part I. Figure 2: The gut microbiota calibrates the immune system. ( 6 ), respectively, report that manipulating the gut microbiota may allow cancer patients to overcome resistance to immunotherapy. More precisely, the study showed that the modification of the gut microbiota affected intestinal mucosal immunity and systemic cytokine circulation (impaired recruitment of CD4+ T cells and GZMB+ cells in tumors). A growing number of studies have revealed how gut microbiota change immune response and influence the efficacy of anticancer immunotherapeutics, e.g. In addition, host immunity regulates the microbiome by altering bacteria-associated . There is an intricate crosstalk among the GM, cancer immune response and immunotherapy (17). This study will further understand the influence and mechanism of the gut microbiota on tumor immunotherapy, and will provide new ideas and theoretical basis for improving the efficacy of tumor immunotherapy by targeting the gut microbiota in the clinic, and benefit more NSCLC patients. A new study summarizes current knowledge about the relationship between the gut microbiota and therapeutic response to immunotherapy, chemotherapy, cancer surgery, and other treatments, pointing to ways the microbiome could be . The role of the gut microbiome in modulating the cancer-immune set-point. With the introduction and colonization of the microbial species in the gut ecosystem, the host immune system has evolved to maintain a mutualistic relationship between microbes and host immunity [].Gut microbiota themselves have a tremendous impact on host physiology and play a central role in the education and function of the host immune system. . In addition, memory Th1 immune responses to B. intestinihominis was shown to predict the prolonged PFS in advanced lung and ovarian cancer patients after platinum-based chemotherapy . Article Google Scholar The Influence of Gut Microbiota on Tumor Immunity Gut microbiota plays an important role in the occurrence and progress of tumors, and the immune system is also the dominant force in tumor control [ 22 ]. Early studies have shown that gut microbiota could stimulate antitumor immune responses by modulating CD8 + T cells [ 28 ], T helper 1 (Th1) [ 29 ], and tumor-associated myeloid cells [ 30 ]. Additionally, short-chain fatty acids . Intestinal microbiota regulates immune responses in the body. The GI microbiota can influence TME and thus tumor growth in both a positive or negative way and can also modulate the immune responses. Gut microbiota influence immunotherapy responses: mechanisms and therapeutic strategies Authors Yuting Lu 1 , Xiangliang Yuan 2 , Miao Wang 1 , Zhihao He 1 , Hongzhong Li 3 , Ji Wang 4 , Qin Li 5 Affiliations 1 Department of Oncology, Beijing Friendship Hospital, Capital Medical University, Beijing, 100050, China.

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