以下文章来源于肥胖世界ObesityWorld ，作者欢迎订阅 肥胖世界ObesityWorld . 《肥胖世界》Obesity World - 同步传真肥胖及代谢国际新学术进展，为医学减重临床、教研人员搭建一座与国际接轨的桥梁，「每医健」旗下内容平台。 近日，范德堡大学的科研团队在《自然》杂志上发表了最新研究。他们发现，肥胖引发的炎性细胞因子会刺激肿瘤相关巨噬细胞（TAM）上 PD-1的表达，削弱了机体对肿瘤的免疫监视能力。虽然这种机制助推了癌症的发展，但同时也让抗PD-1免疫疗法有了更大的施展空间。 肥胖已成为癌症的重要诱因，目前已知有超过13种癌症的发生与肥胖密切相关。作为仅次于吸烟的第二大可预防癌症风险因素，肥胖的危害不 容忽视。 然而，科学家们却发现一个令人困惑的现象：尽管肥胖会加速癌症的发生和进展，但在接受免疫治疗时，肥胖患者却往往表现出"保护效 应"——高BMI人群对免疫疗法的响应率更高，生存预后也更理想。 这究竟是肥胖隐藏的"善意"，还是背后藏着不为人知的机制？ 研究人员将小鼠分为两组，分别喂以低脂饮食（LFD，脂肪提供10%的能量）和高脂饮食（HFD，脂肪占比高达45%），喂食周期从6周龄 ...

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 body's immune surveillance against tumors [8][17]. 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, these mice also showed a notable anti-tumor response when treated with anti-PD-1 antibodies [11][12]. - Analysis of immune cells from HFD mice revealed a decrease in specific CD8+ T cells and an increase in macrophages, with TAM showing altered metabolism and increased PD-1 expression [14][16]. Group 3: Mechanisms and Implications - The study indicates that obesity-related inflammatory factors like INF-γ and TNF-α upregulate PD-1 expression in macrophages, which in turn suppresses their function and reduces T cell activation [17]. - This mechanism suggests that anti-PD-1 inhibitors could effectively counteract the suppressive effects of obesity on TAM, enhancing T cell anti-tumor activity in high BMI populations [18]. Group 4: Future Research Directions - Further investigation is needed to explore the impact of other innate immune cells and different dietary structures on anti-tumor immunity in the context of obesity [18].

Core Insights - Obesity is a significant risk factor for cancer, being linked to over 13 types of cancer and is the second largest preventable cancer risk factor after smoking [6] - Despite obesity accelerating cancer progression, obese patients often show a "protective effect" during immunotherapy, responding better to treatments and having improved survival outcomes [7] Group 1: Research Findings - 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 [8][17] - In experiments with mice, those on a high-fat diet (HFD) exhibited significant weight gain and metabolic abnormalities, and while tumor growth accelerated, they showed a notable response to anti-PD-1 immunotherapy [11][12] - The study found that HFD mice had a decrease in specific CD8+ T cells but an increase in macrophages, with TAM showing altered metabolism and increased PD-1 expression [14][16] Group 2: Mechanisms and Implications - The elevated PD-1 expression on TAM due to obesity-related inflammation suggests a negative feedback mechanism that impairs immune function, yet it also opens avenues for enhanced immunotherapy effectiveness in high BMI populations [18] - The research indicates that targeting PD-1 in obese patients could potentially restore TAM activity and boost T cell anti-tumor responses, highlighting the complex relationship between obesity and cancer immunotherapy [18]