The average age and obesity prevalence are increasing globally. Both aging and metabolic disease burden increase the risk of oral squamous cell carcinoma (OSCC) through profound effects on the immunological and metabolic characteristics within the OSCC tumor microenvironment. While the mechanisms that link aging and obesity to OSCC remain unclear, there is evidence that the antitumor responses are diminished in both conditions. Remarkably, however, immune checkpoint blockade, a form of cancer immunotherapy, remains intact despite the enhanced immunosuppressive tumor microenvironment in the context of either aging or obesity. Herein, we review the current knowledge of how aging and systemic metabolic changes affect antitumor immunity with an emphasis on the role of tumor-associated macrophages that greatly contribute to tumor immunosuppression. Key aspects discussed include the mechanisms of angiogenesis, cytokine release, phagocytosis attenuation, and immune cell recruitment during obesity and aging that create an immune-suppressive tumor microenvironment by recruitment and repolarization of tumor-associated macrophages. Through a deeper appreciation of these mechanisms, the development of novel therapeutic approaches to control OSCC will provide more refined management of the tumor microenvironment in the context of aging and obesity.

中文翻译：

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代谢和衰老对口腔癌抗癌免疫的影响


全球平均年龄和肥胖患病率正在增加。衰老和代谢疾病负担对口腔鳞状细胞癌 (OSCC) 肿瘤微环境内的免疫和代谢特征产生深远影响，从而增加口腔鳞状细胞癌 (OSCC) 的风险。虽然衰老和肥胖与口腔鳞状细胞癌之间的联系机制尚不清楚，但有证据表明，这两种情况下的抗肿瘤反应都会减弱。然而值得注意的是，尽管在衰老或肥胖的背景下免疫抑制肿瘤微环境增强，但免疫检查点阻断（一种癌症免疫疗法）仍然保持完整。在此，我们回顾了目前关于衰老和全身代谢变化如何影响抗肿瘤免疫的知识，重点是肿瘤相关巨噬细胞在肿瘤免疫抑制中的作用。讨论的关键方面包括肥胖和衰老过程中血管生成、细胞因子释放、吞噬作用减弱和免疫细胞招募的机制，这些机制通过肿瘤相关巨噬细胞的招募和复极化创建免疫抑制肿瘤微环境。通过更深入地了解这些机制，开发控制口腔鳞癌的新治疗方法将为衰老和肥胖背景下的肿瘤微环境提供更精细的管理。