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].

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]