Fig. 2: Discovery of IAP inhibitors as immune response sensitizers in LKB1-mut lung cancer and identification of IAP-STING axis as downstream effectors of LKB1-cIAP1 PPI.

A Dose-response curve showing cell viability of isogenic LKB1-WT or KD H1792 cells co-cultured with PBMC. B AUC analysis of PBMC-dose dependent killing curves of lung cancer cells with LKB1-WT (Calu-1, H1299, H1792, and H292) or MUT (A549, H1792, H23 and H460). Each dot represents an individual cell line, and the data were presented as mean ± SD. C Selectivity of compounds in the immune cell-dependent killing of H1755 from the primary screening. D IC₅₀s of six IAP inhibitors in H1755 cancer cell alone culture versus co-culture with PBMC. E Dose-response confirmation of birinapant-induced immune-dependent killing in additional LKB1-mut LUAD cell lines as indicated. F Dose-response curves of birinapant-induced CD8⁺ T and CD56⁺ NK cell-dependent killing in H1755 cell. G STING gene expression in H1755 cells cultured alone or co-cultured with immune cells. The relative mRNA expression was expressed as fold-of-change upon birinapant (50 nM) treatment over normalized DMSO control. H The vialibity of H1755 cells cultured alone or co-cultured with PBMC, or treated with birinapant (100 nM) or in combination with H151 (5 μM). I The cell viability of isogenic H1755 cells expressing non-targeting control (ctrl) shRNA or STING-targeting (STING) shRNA cultured alone or co-cultured with PBMC, or treated with birinapant (100 nM) as indicated. Immunoblot (lower) showing birinapant-induced STING expression in control H1755 cells, but not STING knockdown isogenic cells. J, K Cell viability of stable isogenic H1755 (J) and A549 (K) cells overexpressing STING cultured alone or co-cultured with PBMC. L Immunoblot showing indicated proteins of stable isogenic H1755 and A549 cells overexpressing STING by lentiviral transduction using a pHAGE-STING plasmid. One representative blot from n = 3 independent experiments. Source data are provided as a Source Data file. For (A, B) and (D–G), data are presented as mean ± SD from n = 3 independent experiments; For H-K, data are presented as mean ± SD from n = 4 independent experiments. P-values were calculated by unpaired Student’s t-test with two-tailed analysis without adjustments.