《自然》最新研究：肥胖可导致肿瘤免疫防线受损！

Core Viewpoint - Obesity is a significant risk factor for cancer, being the second leading preventable cause after smoking, with over 13 types of cancer closely linked to obesity [6]. Group 1: Obesity and Cancer - Obesity accelerates the occurrence and progression of cancer, yet obese patients often show a "protective effect" during immunotherapy, responding better to treatments and having improved survival rates [7]. - A recent study from Vanderbilt University published in Nature reveals that inflammatory cytokines induced by obesity stimulate the expression of PD-1 on tumor-associated macrophages (TAM), weakening the immune surveillance against tumors while simultaneously enhancing the efficacy of anti-PD-1 immunotherapy [8][12]. Group 2: Research Findings - In experiments with mice, those on a high-fat diet (HFD) exhibited significant weight gain and metabolic abnormalities, leading to accelerated tumor growth when injected with cancer cells. However, only the HFD group showed notable anti-tumor effects when treated with anti-PD-1 antibodies [11]. - Analysis of immune cells from HFD mice indicated a decrease in specific CD8+ T cells and an increase in macrophages, with significant changes in TAM, including elevated PD-1 expression and altered metabolic states [14][16]. Group 3: Mechanisms and Implications - The study highlights that obesity-related inflammatory factors like INF-γ and TNF-α upregulate PD-1 expression in macrophages through signaling pathways, which in turn suppresses TAM functionality and reduces T cell activation [17]. - This mechanism suggests that anti-PD-1 inhibitors could effectively counteract the suppressive effects of obesity on TAM, thereby enhancing T cell anti-tumor activity in high BMI populations [18]. Group 4: Future Research Directions - Further investigation is needed to explore the roles of other innate immune cells and different dietary structures in the context of tumor immunity and the effects of obesity [18].