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]