Failing CAR T cells express a dysfunctional 41BB CAR T-cell signature. (A) Peripheral blood cells from a patient who received tisagenlecleucel for diffuse large B-cell lymphoma were collected 14 and 100 days after infusion and purified for CAR-expressing cells. (B) UMAP of day-14 and day-100 cells. (C) Expression of CD4 and CD8A in peripheral blood CAR T cells. (D) Overlap between in vitro–defined signature of 41BB-driven dysfunction and genes defining day-100 cell identity. Significance of overlap determined using Fisher exact test. (E) Expression of top 10 driver genes in day-14 and day-100 cells. (F) Log2 fold change in expression of master exhaustion genes in day-100 cells compared with that in day-14 cells. (G) Overlap between genes defining day-100 cell identity and TIL exhaustion signatures. Significance of overlap determined using Fisher exact test.
