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.

中文翻译：

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肥胖和 CD8 T 细胞代谢：对抗肿瘤免疫和癌症免疫治疗结果的影响。

肥胖是许多癌症的既定危险因素，最近发现肥胖会改变基于 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仍不清楚。鉴于 T 细胞代谢与效应器功能紧密相关，了解这些关联至关重要。因此，任何与肥胖相关的 T 细胞生物能变化都可能驱动细胞水平的功能变化，改变代谢组和细胞因子/趋化因子环境，并影响癌症免疫治疗结果。在这里，我们简要概述了存在和不存在实体瘤生长时的 T 细胞代谢，并总结了有关肥胖相关 T 细胞功能和生物能学变化的现有文献。我们还讨论了与宿主肥胖对癌症免疫治疗结果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，我们描述了有前景的药物疗法，这些疗法正在研究其改善 CD8 T 细胞代谢和增强患者癌症免疫治疗结果的能力，无论患者的肥胖状况如何。