Caloric restriction suppresses colorectal tumors and melanoma through CD8 T cells in aged mice

Caloric restriction (CR) has shown the potential to extend lifespan and reduce cancer risk; however, the mechanisms underlying CR-mediated tumor suppression are not fully understood. Here, we investigate age-dependent CR effects on tumor progression and anti-tumor immune responses in a murine CR model. In aged mice, CR, defined as a 30% reduction in caloric intake, significantly suppressed tumor growth in murine syngeneic models of colorectal cancer or melanoma. CR also enhanced tumor infiltration by CD8⁺ T cells, which when depleted limited the tumor-suppressive effects of CR in aged mice. RNA-seq analysis of intratumoral CD8⁺ T cells revealed that CR upregulated the expression of genes associated with T cell function. Furthermore, mechanistic studies of effects of CR on age-related changes in CD8⁺ T cells, and immunohistochemical analysis suggested that normalization of the vasculature in the tumor microenvironment of aged CR mice is accompanied by decreased expression of angiogenic growth factors secreted by intratumoral CD8⁺ T cells. Our findings overall provide insight into age-dependent tumor-suppressive effects of CR and illustrate the essential role of CD8⁺ T cells in CR-mediated tumor suppression.