Fig. 4: PARP14 inhibition promotes pro-inflammatory CD4+ and CD8 + T cell phenotype. | Nature Communications

Fig. 4: PARP14 inhibition promotes pro-inflammatory CD4+ and CD8 + T cell phenotype.

From: PARP14 inhibition restores PD-1 immune checkpoint inhibitor response following IFNγ-driven acquired resistance in preclinical cancer models

Fig. 4

A BALB/C mice were sacrificed and their spleens harvested. Isolated T cells were firstly stimulated with α-CD3 and α-CD28 antibodies, with 1 μM RBN012759 or DMSO. After 48 h, sample aliquots were processed for RT-qPCR analyses, while remaining cells were passaged refreshing the DMSO/ PARP14i for an additional 7 days. Subsequently, cells were re-activated with α-CD3 and α-CD28 antibodies and stained for cytokines after 14 h and for proliferation marker Ki-67 after 96 h. B–E, B Parp14, C Stat1, D Irf1, E Cd274 mRNA expression in cells treated with DMSO (n = 3) or PARP14i (n = 3) relative to the housekeeping gene Gapdh. The data were presented as mean ± S.E.M. and the p-values were determined by two-sided unpaired t-test. F–I Percentage of DMSO (n = 8) and PARP14i (n = 8) pre-treated cells that were F CD4 + IFNG+ (left) and CD8 + IFNG+ (right), G CD4 + TNFA+ (left) and CD8 + TNFA+ (right), H CD4 + LAP+ (left) and CD8 + LAP+ (right), I CD4 + IL-10+ (left) and CD8 + IL-10+ (right). The data were presented as mean ± S.E.M. and the p-values were assessed by two-sided unpaired t-test. J Percentage of DMSO (n = 6) and PARP14i (n = 6) pre-treated cells that were CD8+ Ki- 67+ cells. The data was presented as mean ± S.E.M. and the p-value was assessed by two-sided unpaired t-test. Source data are provided as a Source Data file.

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