CD4 and cancer: T cell PD-1 can mark exhausted cells with decreased functionality versus PD-1− (generally non-exhausted) counterparts.47 In cancer and chronic infection models, PD-1 expressing T cells are most responsive to αPD-L1 and αPD-1 ICI.48,49 In contrast, high levels of T cell PD-1 expression could generate αPD-1 resistance.50 We saw significantly increased PD-1 expression prevalence on splenic CD4+ (Figure 2E) and CD8+ T cell (Figure 2F) subsets and higher splenic PD-1 MFI on aged versus young T cells (Figure S1C), consistent with reports from us and others.51,52