代谢和衰老对口腔癌抗癌免疫的影响

Journal of dental research Pub Date : 2024-09-01 Epub Date: 2024-08-26 DOI:10.1177/00220345241264728
T P M D Santos, W L Hicks, W J Magner, A Al Afif, K L Kirkwood
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摘要

在全球范围内,平均年龄和肥胖率都在不断增加。老龄化和代谢性疾病负担都会对口腔鳞状细胞癌(OSCC)肿瘤微环境中的免疫和代谢特征产生深远影响,从而增加患口腔鳞状细胞癌(OSCC)的风险。虽然将衰老和肥胖与 OSCC 联系起来的机制仍不清楚,但有证据表明,在这两种情况下,抗肿瘤反应都会减弱。但值得注意的是,尽管在衰老或肥胖的情况下肿瘤微环境的免疫抑制作用增强,但免疫检查点阻断这种癌症免疫疗法仍能保持完好。在此,我们回顾了有关衰老和全身代谢变化如何影响抗肿瘤免疫的现有知识,重点是对肿瘤免疫抑制起重要作用的肿瘤相关巨噬细胞的作用。讨论的主要方面包括肥胖和衰老过程中的血管生成、细胞因子释放、吞噬作用减弱和免疫细胞招募机制,这些机制通过招募和重新极化肿瘤相关巨噬细胞来创造免疫抑制性肿瘤微环境。通过更深入地了解这些机制,开发控制 OSCC 的新型治疗方法将能在衰老和肥胖的背景下对肿瘤微环境进行更精细的管理。
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Metabolic and Aging Influence on Anticancer Immunity in Oral Cancer.

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.

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