Fig. 4: PPP2R1A-mutant tumours exhibited improved sensitivity to T cell killing and ICB therapy.

a, The changes in PPP2R1A-specific gRNAs in the reported genome-wide CRISPR immune screens comparing the T-cell-treated group and the control group. b,c, Expression of activated caspase-3 in genetically modified (b) or LB100-treated (c) SKOV3 cell lines after exposure to B7H3 CAR-T cells. Representative results from three independent experiments are shown. shNC, non-targeting control shRNA; shPPP2R1A, PPP2R1A shRNA. d, Overexpression of the PPP2R1A^P179R mutant increased SKOV3 sensitivity to CAR-T-cell-mediated killing. Representative results from four independent replications are shown. e–g, Wild-type and CRISPR-edited HEC50B and OVCAR429 cell lines overexpressing hCD19 were co-cultured with hCD19 CAR-T cells at different effector:target (E:T) ratios, and colony formation (e) and the cancer cell survival (HEC50B (f) and OVCAR429 (g)) was measured at the end point. For each group, four independent replicates were performed. h, Schematic of the study design for PDX models. The diagram was created using BioRender. Hu-BLT, humanized-bone marrow, liver and thymus mice; Hu-EC, human endometrial cancer. i, Tumours from PPP2R1A-mutated PDXs at the end of treatment. j, The weights of tumours from PPP2R1A-mutated PDXs at the end of treatment. Each group included 14 independent repeats. k, Schematic of the study design for syngeneic mouse OCCC models. The diagram was created using BioRender. m-OCCC, mouse OCCC. l,m, The tumour size measured during treatment in the Arid1a^−/−Pik3ca^H1047R (l) or Ppp2r1a^R183QArid1a^−/−Pik3ca^H1047R (m) syngeneic mouse models. n, The tumour weights measured at the end of treatment in the two syngeneic models. In l–n, each group included five independent replicates. Data are mean ± s.e.m. P values were calculated using two-sided Student’s t-tests (j) and repeated-measures analysis of variance (ANOVA) with Tukey’s test for pairwise comparisons (b–d and l–n).

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