first_pagesettingsOrder Article Reprints Open AccessReview Exploring the Role of the Gut Microbiota in Modulating Colorectal Cancer Immunity by Nikolay K. Shakhpazyan 1,*ORCID,Liudmila M. Mikhaleva 1ORCID,Arkady L. Bedzhanyan 2ORCID,Zarina V. Gioeva 1,Alexander I. Mikhalev 3,Konstantin Y. Midiber 1,4ORCID,Valentina V. Pechnikova 1ORCID andAndrey E. Biryukov 1 1 Avtsyn Research Institute of Human Morphology, Petrovsky National Research Center of Surgery, 119435 Moscow, Russia 2 Department of Abdominal Surgery and Oncology II (Coloproctology and Uro-Gynecology), Petrovsky National Research Center of Surgery, 119435 Moscow, Russia 3 Department of Hospital Surgery No. 2, Pirogov Russian National Research Medical University, 117997 Moscow, Russia 4 Institute of Medicine, Peoples’ Friendship University of Russia named after Patrice Lumumba, 6 Miklukho-Maklaya St., 117198 Moscow, Russia * Author to whom correspondence should be addressed. Cells 2024, 13(17), 1437; https://doi.org/10.3390/cells13171437 Submission received: 24 June 2024 / Revised: 26 July 2024 / Accepted: 23 August 2024 / Published: 27 August 2024 (This article belongs to the Special Issue Tumor Immune Microenvironment for Effective Therapy II) Downloadkeyboard_arrow_down Browse Figures Review Reports Versions Notes Abstract The gut microbiota plays an essential role in maintaining immune homeostasis and influencing the immune landscape within the tumor microenvironment. This review aims to elucidate the interactions between gut microbiota and tumor immune dynamics, with a focus on colorectal cancer (CRC). The review spans foundational concepts of immuno-microbial interplay, factors influencing microbiome composition, and evidence linking gut microbiota to cancer immunotherapy outcomes. Gut microbiota modulates anti-cancer immunity through several mechanisms, including enhancement of immune surveillance and modulation of inflammatory responses. Specific microbial species and their metabolic byproducts can significantly influence the efficacy of cancer immunotherapies. Furthermore, microbial diversity within the gut microbiota correlates with clinical outcomes in CRC, suggesting potential as a valuable biomarker for predicting response to immunotherapy. Conclusions: Understanding the relationship between gut microbiota and tumor immune responses offers potential for novel therapeutic strategies and biomarker development. The gut microbiota not only influences the natural history and treatment response of CRC but also serves as a critical modulator of immune homeostasis and anti-cancer activity. Further exploration into the microbiome’s role could enhance the effectiveness of existing treatments and guide the development of new therapeutic modalities.