Amitrano Andrea M, Kim Minsoo
Department of Pathology, University of Rochester Medical Center, Rochester, NY 14642, USA.
Department of Microbiology and Immunology, David H. Smith Center for Vaccine Biology and Immunology, University of Rochester Medical Center, Rochester, NY 14642, USA.
Immune Netw. 2023 Jan 27;23(1):e9. doi: 10.4110/in.2023.23.e9. eCollection 2023 Feb.
Cancer immunotherapies continue to face numerous obstacles in the successful treatment of solid malignancies. While immunotherapy has emerged as an extremely effective treatment option for hematologic malignancies, it is largely ineffective against solid tumors due in part to metabolic challenges present in the tumor microenvironment (TME). Tumor-infiltrating CD8 T cells face fierce competition with cancer cells for limited nutrients. The strong metabolic suppression in the TME often leads to impaired T-cell recruitment to the tumor site and hyporesponsive effector functions via T-cell exhaustion. Growing evidence suggests that mitochondria play a key role in CD8 T-cell activation, migration, effector functions, and persistence in tumors. Therefore, targeting the mitochondrial metabolism of adoptively transferred T cells has the potential to greatly improve the effectiveness of cancer immunotherapies in treating solid malignancies.
癌症免疫疗法在实体恶性肿瘤的成功治疗中仍然面临众多障碍。虽然免疫疗法已成为血液系统恶性肿瘤极为有效的治疗选择，但在很大程度上对实体瘤无效，部分原因是肿瘤微环境（TME）中存在代谢挑战。肿瘤浸润性CD8 T细胞与癌细胞在有限营养物质方面面临激烈竞争。TME中的强烈代谢抑制通常会导致T细胞募集到肿瘤部位受损，并通过T细胞耗竭导致效应功能反应低下。越来越多的证据表明，线粒体在CD8 T细胞的激活、迁移、效应功能以及在肿瘤中的持久性中起关键作用。因此，靶向过继转移T细胞的线粒体代谢有可能极大地提高癌症免疫疗法在治疗实体恶性肿瘤中的有效性。
