Comparison of IKCscore and PD-L1 in predicting immunotherapy monotherapy and combined therapy
(A) Rate of response to ICBs in different PD-L1 expression groups, including level 0, level 1, and level 2 in the NFH cohort. PD-L1 level 0: <1%; level 1: 1–49%; level 2: ≥50%.
(B) Rate of response to ICBs in high and low IKCscore groups in the NFH cohort.
(C) IKCscore was positively associated with PD-L1 expression level (Kruskal−Wallis, p = 0.018).
(D and E) In IMvigor210 study, tumor tissue samples were scored through immunohistochemistry (IHC) for PD-L1 expression on tumor-infiltrating immune cells (IC), which included macrophages, dendritic cells and lymphocytes. Specimens were scored as IHC IC0, IC1, IC2, or IC3 if <1%, ≥1% but <5%, ≥5% but <10%, or ≥10% of IC were PD-L1 positive, respectively. The PD-L1 expression on tumor cells (TC) was also conducted. Specimens were scored as IHC TC0, TC1, TC2, or TC3 if <1%, ≥1% but <5%, ≥5% but <50%, or ≥50% of TC were PD-L1 positive, respectively. PD-L1 expression, both IC (D) and TC (E), are positively correlated with IKCscore in the IMvigor210 cohort. IC0 and TC0 tumors have the lowest IKCscore compared to IC1, IC2+, TC1, and TC2+ (IC: Kruskal−Wallis, p < 2.2e−16; TC: Kruskal−Wallis, p = 1.8e−11).
(F) ROC curve of IKCscore, continuous PD-L1 expression, PD-L1 level, and PD-L1 binary in NFH cohort with PD-L1 IHC results who received anti-PD-1 inhibitor monotherapy (AUC = 0.929, 0.691, 0.643, 0.571, respectively).
(G) ROC curve of IKCscore, continued PD-L1 expression, PD-L1 level, and PD-L1 binary in NFH cohort with PD-L1 IHC results who received anti-PD-1 inhibitor plus chemotherapy combination therapy (AUC = 0.851, 0.646, 0.646, 0.542, respectively).
(H) The IKCscore distribution of case 1 patient and the typical CT image at the baseline and PR times.
(I) ROC curve of IKCscore, continuous PD-L1 expression, PD-L1 level, and PD-L1 binary in NFH validation cohort receiving anti-PD-1 inhibitor plus chemotherapy combination therapy (AUC = 0.857, 0.810, 0.679, 0.429, respectively).