Figure 4. Shifts in the tumor immune infiltrate affect anti-tumor CD8⁺ T cell function in distinct systemic conditions.

In addition to CD8⁺ T cells, the TME contains other immune populations, some of which are immunostimulatory (e.g. M1-polarized macrophages), while others are suppressive (e.g. M2-polarized macrophages, MDSCs and Tregs). In aging, enhanced MDSC numbers and potentially M2 macrophages contribute to immunosuppression, resulting in a reduced anti-tumor CD8⁺ T cell response. Tregs may be either increased or decreased with aging. Similar shifts in cellular populations in the TME exist with obesity. In dietary restriction, Treg and MDSC numbers are reduced while macrophage polarization is shifted toward the M1 phenotype, resulting in an increased anti-tumor CD8⁺ T cell response. MDSC, myeloid-derived suppressor cell. TME, tumor microenvironment. Treg, regulatory T cell.