Interaction between gut microbiota and T cell immunity in colorectal cancer

• Published in: Autoimmunity reviews Vol. 24; no. 6; p. 103807
• Main Authors: Jing, Zhuang, Yinhang, Wu, Jian, Chu, Zhanbo, Qu, Xinyue, Wu, Shuwen, Han
• Format: Journal Article
• Language: English
• Published: Netherlands Elsevier B.V 30.05.2025
• Subjects: Allergy and Immunology; Animals; Colorectal cancer; Colorectal Neoplasms - immunology; Colorectal Neoplasms - metabolism; Colorectal Neoplasms - microbiology; Colorectal Neoplasms - therapy; Gastrointestinal Microbiome - immunology; Gut microbiota; Humans; Metabolites; T cell immunity; T-Lymphocytes - immunology; T-Lymphocytes - metabolism; Tumor Microenvironment - immunology; Gut microbiota; intestinal epithelial cells; effector memory; inflammatory bowel diseases; Clostridiales strains; Colorectal cancer; inhibitors of differentiation 2; tertiary lymphoid structures; Lactobacillus rhamnosus GG; NLR family pyrin domain containing 3; bone marrow-derived dendritic cells; Sini Decoction; azoxymethane; tumor-associated macrophages; Abelmoschus manihot; box transcription factor 13; all-trans-retinoic acid; mesenteric lymph node; Metabolites; ketogenic diet; free fatty acid receptor 2; interleukin; metagenome-wide association study; hepatocellular carcinoma; N-3-oxododecanoyl-L-homoserine lactone; quorum sensing; Toll-like receptor 2; sex-determining region Y; Helicobacter Aciclocus; dextran sulfate sodium; T-helper 1 cells; traditional Chinese medicine; inflammatory bowel disease-associated CRCs; autoinducer-2; germinal center; tissue resident memory T; histone deacetylase; high-fatty-diet; regulatory T cells; Fusobacterium nucleatum; polymorphonuclear-myeloid-derived suppressor cells; T cell immunity; follicular helper T; IPA; Quxie Capsule; short-chain fatty acids; peroxisome proliferator-activated receptor gamma; transforming growth factor-β-activated kinase-1; Indole-3-Propionic Acid; TAM; HFD; IECs; TRM; MLN; atRA; Tfh; FFAR2; Th1; BM-DCs; QS; IL; DSS; QX; EM; HCC; AM; LGG; PPARγ; MGWAS; OdDHL; CRC; IBD-CRCs; PMN-MDSCs; TLR2; HDAC; TCM; SND; IBD; AI-2; TAK1; CC4; NLRP3; KD; SRY; Sox13; GC; TLSs; AOM; Tregs; Fn; Hhep; ID2; SCFAs
• ISSN: 1568-9972; 1873-0183
• DOI: 10.1016/j.autrev.2025.103807

This review delves into the complex and multi-layered mechanisms that govern the interaction between gut microbiota and T cells in the context of colorectal cancer (CRC), revealing a novel “microbiota-immune regulatory landscape” within the tumor microenvironment. As CRC progresses, the gut microbiota experiences a significant transformation in both its composition and metabolic patterns. On one hand, specific microbial entities within the gut microbiota can directly engage with T cells, functioning as “immunological triggers” that shape T-cell behavior. Simultaneously, microbial metabolites, such as short-chain fatty acids and bile acids, serve as “molecular regulators” that intricately govern T-cell function and differentiation, fine-tuning the immune response. On the other hand, the quorum-sensing mechanism, a recently recognized communication network among bacteria, also plays a pivotal role in orchestrating T-cell immunity. Additionally, the gut microbiota forms an intriguing connection with the neuro-immune regulatory axis, a largely unexplored “territory” in CRC research. Regarding treatment strategies, a diverse array of intervention approaches—including dietary modifications, the utilization of probiotics, bacteriophages, and targeted antibiotic therapies—offer promising prospects for restoring the equilibrium of the gut microbiota, thereby acting as “ecosystem renovators” that impede tumor initiation and progression. Nevertheless, the current research landscape in this field is fraught with challenges. These include significant variations in microbial composition, dietary preferences, and tumor microenvironments among individuals, a lack of large-scale cohort studies, and insufficient research that integrates tumor mutation analysis, gut microbiota investigations, and immune microenvironment evaluations. This review emphasizes the necessity for future research efforts to seamlessly incorporate multiple factors and utilize bioinformatics analysis to construct a more comprehensive “interactive map” of the gut microbiota-T cell relationship in CRC. The aim is to establish a solid theoretical basis for the development of highly effective and personalized treatment regimens, ultimately transforming the therapeutic approach to CRC.