PD1 deletion reverses exhaustion in mice in vivo and predicts worse prognosis in patients. (A) Microarray based expression analysis of exhaustion-associated genes in ITK-SYK–driven murine CD4⁺ T cells compared with nontransformed naive T cells. Each column represents 1 biological replicate. Color bar (right) indicates expression z score. T-NHL, T-cell non-Hodgkin lymphoma. (B) Gene set enrichment analysis (GSEA) of transcripts derived from cells of PD1 competent ITK-SYK^CD4CreERT2 animals (PD1^+/+) in comparison with cells derived from PD1-deficient ITK-SYK^CD4CreERT2;PD1^−/− mice (PD1^−/−). ITK-SYK–expressing cells were FACS-sorted from both genotypes at 5 days after tamoxifen treatment. (C) Percentage of PD1-deleted samples by stage across all patients with MF or SS (n = 49). χ² test for trend. (D-E) Kaplan-Meier survival curves of SS stage IV (D) and MF stages II and III (E) according to PD1 genotypes. For stage IV SS, survival information for patients with PD1 genetic status from published studies are included.^3,23 The starting date is the date of diagnosis, and the ending date is the date of death or transplantation; n indicates number of samples in each group. The P value was calculated by log-rank (Mantel-Cox) test.