DiPalma Michelle P, Blattman Joseph N
School of Life Sciences, Arizona State University, Tempe, AZ, United States.
Biodesign Institute, Center for Immunotherapy, Vaccines and Virotherapy (CIVV), Arizona State University, Tempe, AZ, United States.
Front Cell Dev Biol. 2023 Mar 17;11:1141215. doi: 10.3389/fcell.2023.1141215. eCollection 2023.
Insights into the effect of the microbiome's composition on immune cell function have recently been discerned and further characterized. Microbiome dysbiosis can result in functional alterations across immune cells, including those required for innate and adaptive immune responses to malignancies and immunotherapy treatment. Dysbiosis can yield changes in or elimination of metabolite secretions, such as short-chain fatty acids (SCFAs), from certain bacterial species that are believed to impact proper immune cell function. Such alterations within the tumor microenvironment (TME) can significantly affect T cell function and survival necessary for eliminating cancerous cells. Understanding these effects is essential to improve the immune system's ability to fight malignancies and the subsequent efficacy of immunotherapies that rely on T cells. In this review, we assess typical T cell response to malignancies, classify the known impact of the microbiome and particular metabolites on T cells, discuss how dysbiosis can affect their function in the TME then further describe the impact of the microbiome on T cell-based immunotherapy treatment, with an emphasis on recent developments in the field. Understanding the impact of dysbiosis on T cell function within the TME can carry substantial implications for the design of immunotherapy treatments and further our understanding of factors that could impact how the immune system combats malignancies.
最近,人们对微生物组组成对免疫细胞功能的影响有了新的认识并进行了进一步的特征描述。微生物组生态失调可导致免疫细胞功能发生改变,包括对恶性肿瘤和免疫治疗产生先天性和适应性免疫反应所需的细胞。生态失调会导致某些细菌物种的代谢物分泌发生变化或消除,如短链脂肪酸(SCFAs),而这些代谢物被认为会影响免疫细胞的正常功能。肿瘤微环境(TME)内的此类改变会显著影响消除癌细胞所需的T细胞功能和存活。了解这些影响对于提高免疫系统对抗恶性肿瘤的能力以及依赖T细胞的免疫疗法的后续疗效至关重要。在本综述中,我们评估了T细胞对恶性肿瘤的典型反应,分类了微生物组和特定代谢物对T细胞的已知影响,讨论了生态失调如何影响它们在肿瘤微环境中的功能,然后进一步描述了微生物组对基于T细胞的免疫治疗的影响,重点介绍了该领域的最新进展。了解生态失调对肿瘤微环境中T细胞功能的影响对于免疫治疗的设计具有重要意义,并能进一步加深我们对可能影响免疫系统对抗恶性肿瘤方式的因素的理解。