Pasquarelli-do-Nascimento Gabriel, Machado Sabrina Azevedo, de Carvalho Juliana Maria Andrade, Magalhães Kelly Grace
Laboratory of Immunology and Inflammation, Department of Cell Biology, University of Brasilia, DF, Brazil.
Immunother Adv. 2022 Jun 24;2(1):ltac015. doi: 10.1093/immadv/ltac015. eCollection 2022.
Many different types of cancer are now well known to have increased occurrence or severity in individuals with obesity. The influence of obesity on cancer and the immune cells in the tumor microenvironment has been thought to be a pleiotropic effect. As key endocrine and immune organs, the highly plastic adipose tissues play crucial roles in obesity pathophysiology, as they show alterations according to environmental cues. Adipose tissues of lean subjects present mostly anti-inflammatory cells that are crucial in tissue remodeling, favoring uncoupling protein 1 expression and non-shivering thermogenesis. Oppositely, obese adipose tissues display massive proinflammatory immune cell infiltration, dying adipocytes, and enhanced crown-like structure formation. In this review, we discuss how obesity can lead to derangements and dysfunctions in antitumor CD8+ T lymphocytes dysfunction. Moreover, we explain how obesity can affect the efficiency of cancer immunotherapy, depicting the mechanisms involved in this process. Cancer immunotherapy management includes monoclonal antibodies targeting the immune checkpoint blockade. Exhausted CD8+ T lymphocytes show elevated programmed cell death-1 (PD-1) expression and highly glycolytic tumors tend to show a good response to anti-PD-1/PD-L1 immunotherapy. Although obesity is a risk factor for the development of several neoplasms and is linked with increased tumor growth and aggressiveness, obesity is also related to improved response to cancer immunotherapy, a phenomenon called the obesity paradox. However, patients affected by obesity present higher incidences of adverse events related to this therapy. These limitations highlight the necessity of a deeper investigation of factors that influence the obesity paradox to improve the application of these therapies.
现在人们已经熟知，许多不同类型的癌症在肥胖个体中的发生率或严重程度会增加。肥胖对癌症及肿瘤微环境中免疫细胞的影响被认为是一种多效性效应。作为关键的内分泌和免疫器官，高度可塑性的脂肪组织在肥胖病理生理学中起着至关重要的作用，因为它们会根据环境线索发生改变。瘦人的脂肪组织主要呈现抗炎细胞，这些细胞在组织重塑中至关重要，有利于解偶联蛋白1的表达和非寒战产热。相反，肥胖者的脂肪组织表现出大量促炎免疫细胞浸润、死亡的脂肪细胞以及增强的冠状结构形成。在这篇综述中，我们讨论肥胖如何导致抗肿瘤CD8 + T淋巴细胞功能紊乱和功能障碍。此外，我们解释肥胖如何影响癌症免疫治疗的效率，描述这一过程中涉及的机制。癌症免疫治疗管理包括针对免疫检查点阻断的单克隆抗体。耗竭的CD8 + T淋巴细胞显示程序性细胞死亡蛋白1（PD - 1）表达升高，而高度糖酵解的肿瘤往往对抗PD - 1/PD - L1免疫治疗表现出良好反应。尽管肥胖是多种肿瘤发生的危险因素，且与肿瘤生长和侵袭性增加有关，但肥胖也与癌症免疫治疗反应改善有关，这一现象被称为肥胖悖论。然而，肥胖患者出现与这种治疗相关的不良事件的发生率更高。这些局限性凸显了深入研究影响肥胖悖论的因素以改善这些治疗应用的必要性。
