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. Author manuscript; available in PMC: 2022 Dec 9.
Published in final edited form as: Cell. 2021 Dec 2;184(25):6081–6100.e26. doi: 10.1016/j.cell.2021.11.016

Figure 4: In vivo relevance of CAR and TCR T cell dysfunction signature and the NK-like phenotype.

Figure 4:

(A) Time-related changes in NK-associated molecules and PD-1 and CD28 on surCARpos and surCARneg CD8+ T cells during CAE. iNKT are defined as cells with Vα24-Jα18 specific TCRs. Data from ND150 is shown. (B) Experimental design of the recurrent AsPC-1 mouse model. (C) AsPC-1 tumor growth volumes in M5CAR T-treated mice. Red arrows indicate tumors analyzed after recurrence. (D) NK-associated molecules expression in CD8 day 0 product (top) and TILs from a representative AsPC-1 recurrent tumor (bottom). (E) Average expression of NK-associated molecules on CD8 T cells in day 0 product and in three recurrent tumors. Each datapoint represents a single mouse for recurrent tumor data and a single technical replicate staining for day 0 product. Color code for mice data is matched with Figure 4C. (F) PD-1, LAG3, and TIM3 expression in CD8 day 0 product (top) and TILs from a representative AsPC-1 recurrent tumor (bottom). (G) Average expression of checkpoint receptors PD-1, LAG3, and TIM3 in CD8 T cells. Each datapoint represents a single mouse for recurrent tumor data and a single technical replicate staining for day 0 product. Color code for mice data is matched with Figure 4C. (H) CD56 expression in CD8+ surCARpos T cells isolated from DLBCL patients at the peak of CTL019 expansion. (I) Expression of NK-associated molecules and PD-1 on CD8+ surCARpos T cells in day 0 product and day 27 peripheral blood T cells from a patient with DLBCL (#13413–39). (J) Timeline showing the experimental design of NY-ESO-1 TIL mouse model. (K) Heatmap of dysfunction signature genes in NY-ESO-1 reactive CD8+ TILs along with blood (CD8+CD45RO+ T cells) and day 0 infused product. See also Figure S6. Data from (E) and (G) is shown as mean ± SEM and significance were assessed by two-way ANOVA plus Sidak test.