Fig. 3: IAP inhibitors synergize with IFNγ to induce STING expression in LKB1-mut cells. | Nature Communications

Fig. 3: IAP inhibitors synergize with IFNγ to induce STING expression in LKB1-mut cells.

From: Uncovering the rewired IAP-JAK regulatory axis as an immune-dependent vulnerability of LKB1-mutant lung cancer

Fig. 3

A DEGs in H1755 cell treated with birinapant (50 nM) in cancer cells alone culture or co-cultured with PBMC (n = 3 technical replicates). B Gene ontology analysis showing DEGs-associated top-enriched pathways. C, D STING mRNA (C) and proteins expression (D) in A549 cells upon birinapant (500 nM) treatment without (-) or with (+) IFNγ (1 ng/mL) for 24 h. E, F STING mRNA (E) and protein expression (F) in A549 cells upon treatment with IAP inhibitors (500 nM) or in combination with IFNγ (1 ng/mL) for 24 h. G STING expression in A549 STING-HiBiT cells treated with IAP inhibitors (500 nM) or in combination with IFNγ (1 ng/mL) for 24 h (n = 4 independent experiments). H Dose-response curve of birinapant-induced STING expression in A549 STING-HiBiT cells in the presence of 1 ng/mL IFNγ. I STING expression in isogenic cIAP1 knockdown A549 cells treated with 1 ng/mL IFNγ for 24 h. J, K STING protein (J) and mRNA (K) expression in A549 cells treated with birinapant (500 nM) and IFNγ (1 ng/mL) in combination with JAK inhibitors, oclacitinib (Ocla, 10 μM) and tofacitinib (Tofa, 10 μM), or RIPK inhibitor, necrostatin-1 (Nec-1, 10 μM). L STING-HiBiT signal in genetically engineered A549 cells treated with birinapant (500 nM) and IFNγ (1 ng/mL) in combination with Ocla(10 μM) and Tofa (10 μM) (n = 4 independent experiments). M, N STING expression in isogenic JAK1 (M) or STAT1 (N) knockdown (KD) A549 cells treated with birinapant (500 nM) and 1 ng/mL IFNγ for 24 h. O Viability of H1755 cells in cancer cell alone culture or co-culture with PBMC in combination with Ocla(10 μM) and Tofa (10 μM). Source data are provided as a Source Data file. For (C, E, H, K, and O), data are presented as mean ± SD of n = 3 independent experiments. For (D, F, I, J and M, N), data are presented as one representative blot of n = 3 independent experiments. P-values were calculated by unpaired Student’s t-test with two-tailed analysis without adjustments.

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