Department of Nutrition Sciences, University of Alabama at Birmingham, Birmingham, Alabama.
Department of Urology, The University of Iowa, Iowa City, Iowa.
Immunol Rev. 2020 May;295(1):203-219. doi: 10.1111/imr.12849. Epub 2020 Mar 10.
Obesity is an established risk factor for many cancers and has recently been found to alter the efficacy of T cell-based immunotherapies. Currently, however, the effects of obesity on immunometabolism remain unclear. Understanding these associations is critical, given the fact that T cell metabolism is tightly linked to effector function. Thus, any obesity-associated changes in T cell bioenergetics are likely to drive functional changes at the cellular level, alter the metabolome and cytokine/chemokine milieu, and impact cancer immunotherapy outcomes. Here, we provide a brief overview of T cell metabolism in the presence and absence of solid tumor growth and summarize current literature regarding obesity-associated changes in T cell function and bioenergetics. We also discuss recent findings related to the impact of host obesity on cancer immunotherapy outcomes and present potential mechanisms by which T cell metabolism may influence therapeutic efficacy. Finally, we describe promising pharmaceutical therapies that are being investigated for their ability to improve CD8 T cell metabolism and enhance cancer immunotherapy outcomes in patients, regardless of their obesity status.
肥胖是许多癌症的既定风险因素，最近还发现它会改变基于 T 细胞的免疫疗法的疗效。然而，目前肥胖对免疫代谢的影响尚不清楚。鉴于 T 细胞代谢与效应功能密切相关，了解这些关联至关重要。因此，T 细胞生物能量学中任何与肥胖相关的变化都可能在细胞水平上导致功能变化，改变代谢组、细胞因子/趋化因子环境，并影响癌症免疫治疗的结果。在这里，我们简要概述了在存在和不存在实体瘤生长的情况下 T 细胞的代谢，并总结了目前关于肥胖对 T 细胞功能和生物能量学的影响的相关文献。我们还讨论了与宿主肥胖对癌症免疫治疗结果的影响相关的最新发现，并提出了 T 细胞代谢可能影响治疗效果的潜在机制。最后，我们描述了一些有前途的药物治疗方法，这些方法正在被研究，以提高 CD8 T 细胞的代谢，并在无论患者是否肥胖的情况下，增强癌症免疫治疗的效果。
