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

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 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.