Fig 1.
Examples of PD-L1 staining, scoring criteria, prevalence and overlap between PD-L1 expression on TC and IC and prevalence of CD8 infiltration in the tumor center in NSCLC.
(A) PD-L1 expression by IHC on both TC and IC for each subgroup. (B) PD-L1 IHC scoring criteria on TC and IC (3) (C) Overall prevalence of overlapping PD-L1 subgroups. (D) Percentages in Venn diagrams represent the prevalence of PD-L1 expression by TC and IC in overlapping subgroups. (E) Overall prevalence of CD8 infiltration in the tumor center.
Table 1.
Patients’ and tumor characteristics of the non-small cell lung cancer cohort.
Fig 2.
Associations of mRNA expression of CD274, infiltration of CD8 and the IFNγ response signature in non-overlapping PD-L1 expressing subgroups.
(A) Relative mRNA expression of CD274 and CD8 infiltration in TC3 tumors based on various levels of IC (n = 39). (B) Relative mRNA expression of CD274 and CD8 infiltration in IC3 tumors based on various levels of TC (n = 83). (C) Relative mRNA expression of CD274 and CD8 infiltration in TC0 tumors based on various levels of IC (n = 351). (D) Relative mRNA expression of the IFNγ response signature in non-overlapping PD-L1 subgroups: TC0&IC0, TC0/IC123 and TC123/IC123 (n = 530). (E) The actual minus the expected relative mRNA expression of the IFNγ response signature comparing TC negative to TC positive samples for each non-overlapping IC-subgroup. Expected IFNγ response signature expression was obtained from the level of Teff signature expression based on their linear relationship. ns = non significant, * p = 0.01–0.05, ** p < 0.01, *** p < 0.001.
Fig 3.
The effect of PD-L1 expression, the expression of CD8A and the Teff signature on OS.
(A) Forest plot for overlapping PD-L1 expressing subgroups show no improved OS for higher PD-L1 expression; stratified for tumor stage. (B) Forest plot and Kaplan Meier curve for CD8A expression show improved OS for the highest two quartiles; stratified for tumor stage (HR 0.72 (95%CI 0.55–0.95; p = 0.016)). (C) Forest plot and Kaplan Meier curve for quartiles of the Teff signature show improved OS for the highest quartile; stratified for tumor stage (HR 0.68 (95%CI 0.49–0.96; p = 0.027)).