Obesity is a major risk factor for cancer, but the mechanisms linking obesity to cancer remain unclear. This study investigates how obesity-related immune dysfunction affects tumor immunity and cancer risk. Using a mouse model of diet-induced obesity, the researchers found that obesity impairs CD8+ T cell function, which is critical for detecting and eliminating cancer cells. However, weight loss through dietary restriction or semaglutide treatment can restore T cell function and improve responses to immunotherapy. In mice exposed to a carcinogen, obesity-related immune dysfunction leads to higher sarcoma incidence, but impaired immunoediting in obese mice enhances tumor immunogenicity, making them more sensitive to immunotherapy. These findings suggest that obesity-related immune dysfunction contributes to cancer risk and may explain the "obesity paradox" observed in clinical immunotherapy settings, where obese patients sometimes have better survival outcomes. The study also shows that diet-induced weight loss can restore antitumor immunity, while semaglutide-induced weight loss alone is insufficient to improve tumor immunity. Obesity-related immune dysfunction compromises immune surveillance, leading to less efficient tumor editing and more immunogenic tumors. These results highlight the complex interplay between obesity, immunity, and cancer, and suggest that restoring metabolic health through diet and weight loss may be a promising strategy to improve antitumor immunity in obese individuals.Obesity is a major risk factor for cancer, but the mechanisms linking obesity to cancer remain unclear. This study investigates how obesity-related immune dysfunction affects tumor immunity and cancer risk. Using a mouse model of diet-induced obesity, the researchers found that obesity impairs CD8+ T cell function, which is critical for detecting and eliminating cancer cells. However, weight loss through dietary restriction or semaglutide treatment can restore T cell function and improve responses to immunotherapy. In mice exposed to a carcinogen, obesity-related immune dysfunction leads to higher sarcoma incidence, but impaired immunoediting in obese mice enhances tumor immunogenicity, making them more sensitive to immunotherapy. These findings suggest that obesity-related immune dysfunction contributes to cancer risk and may explain the "obesity paradox" observed in clinical immunotherapy settings, where obese patients sometimes have better survival outcomes. The study also shows that diet-induced weight loss can restore antitumor immunity, while semaglutide-induced weight loss alone is insufficient to improve tumor immunity. Obesity-related immune dysfunction compromises immune surveillance, leading to less efficient tumor editing and more immunogenic tumors. These results highlight the complex interplay between obesity, immunity, and cancer, and suggest that restoring metabolic health through diet and weight loss may be a promising strategy to improve antitumor immunity in obese individuals.