Critical role of the CD44 <sup>low</sup> CD62L <sup>low</sup> CD8 <sup>+</sup> T cell subset in restoring antitumor immunity in aged mice
Yuka Nakajima, Kenji Chamoto, Takuma Oura, Tasuku Honjo
Abstract
Significance Although aging is known to suppress antitumor immunity, the precise underlying mechanism remains largely unknown. Here, we found that the inefficient generation of CD44 low CD62L low CD8 + T cell subset (P4), pre-effector–like T cells, could explain the resistance to PD-1 blockade antitumor therapy in aged mice. Elevated expression of CD45RB in aged naive CD8 + T cells appears to inhibit TCR signaling, resulting in fewer P4 cells, a subset with high expression of 1C metabolic genes. This decrease in P4 cells and antitumor activity was rescued by strong immunogenic stimulation by nonself cells. These findings provide valuable insights into the mechanism underlying age-induced suppression of antitumor immunity, which may provide a basis for the development of therapeutic strategies for elderly cancer patients.