Flory Madison, Bravo Paloma, Alam Ashfaqul
Department of Microbiology, Immunology and Molecular Genetics, University of Kentucky, Lexington, KY, USA.
Department of Biology, Carleton College, Northfield, MN, USA.
Immunometabolism (Cobham). 2024 Nov 28;6(4):e00050. doi: 10.1097/IN9.0000000000000050. eCollection 2024 Oct.
Colorectal cancer (CRC) is highly prevalent, accounting for approximately one-tenth of cancer cases and deaths globally. It stands as the second most deadly and third most common cancer type. Although the gut microbiota has been implicated in CRC carcinogenesis for the last several decades, it remains one of the least understood risk factors for CRC development, as the gut microbiota is highly diverse and variable. Many studies have uncovered unique microbial signatures in CRC patients compared with healthy matched controls, with variations dependent on patient age, disease stage, and location. In addition, mechanistic studies revealed that tumor-associated bacteria produce diverse metabolites, proteins, and macromolecules during tumor development and progression in the colon, which impact both cancer cells and immune cells. Here, we summarize microbiota's role in tumor development and progression, then we discuss how the metabolic alterations in CRC tumor cells, immune cells, and the tumor microenvironment result in the reprogramming of activation, differentiation, functions, and phenotypes of immune cells within the tumor. Tumor-associated microbiota also undergoes metabolic adaptation to survive within the tumor environment, leading to immune evasion, accumulation of mutations, and impairment of immune cells. Finally, we conclude with a discussion on the interplay between gut microbiota, immunometabolism, and CRC, highlighting a complex interaction that influences cancer development, progression, and cancer therapy efficacy.
结直肠癌（CRC）非常普遍，约占全球癌症病例和死亡人数的十分之一。它是第二大致命且第三常见的癌症类型。尽管在过去几十年中肠道微生物群已被认为与结直肠癌的致癌作用有关，但它仍然是结直肠癌发展中最不为人所了解的风险因素之一，因为肠道微生物群高度多样且易变。与健康对照相比，许多研究发现了CRC患者独特的微生物特征，其差异取决于患者年龄、疾病阶段和位置。此外，机制研究表明，肿瘤相关细菌在结肠肿瘤发生和发展过程中产生多种代谢产物、蛋白质和大分子，这会影响癌细胞和免疫细胞。在这里，我们总结了微生物群在肿瘤发生和发展中的作用，然后讨论了CRC肿瘤细胞、免疫细胞和肿瘤微环境中的代谢改变如何导致肿瘤内免疫细胞的激活、分化、功能和表型重编程。肿瘤相关微生物群也会进行代谢适应以在肿瘤环境中生存，从而导致免疫逃逸、突变积累和免疫细胞受损。最后，我们讨论了肠道微生物群、免疫代谢和CRC之间的相互作用，强调了影响癌症发展、进展和癌症治疗疗效的复杂相互作用。
