免疫相关微环境的差异决定晚期 NSCLC 患者 PD-1/PD-L1 阻断的疗效

We retrospectively reviewed patients with advanced NSCLC treated with anti-PD-1/PD-L1 therapy between 2015 and 2019. We investigated the association between the efficacy of anti-PD-1/PD-L1 therapy, the types of TME based on PD-L1 (clone: 22C3) expression, the density of CD8-positive TILs assessed by immunohistochemistry, and mutational profiles by next-generation sequencing.

Overall, 228 patients were included in the analysis. The patients were classified into the following four groups: type I: PD-L1 High (tumor proportion score 50%)/TIL High ( 85/mm 2 ; n = 73); type II: PD-L1 Low (tumor proportion score < 50%)/TIL Low (<85/mm 2 ; n = 70); type III: PD-L1 High /TIL Low (n = 37); and type IV: PD-L1 Low /TIL High (n = 48). The objective response rate (ORR) and progression-free survival (PFS) of anti-PD-1/PD-L1 therapy clearly differed according to the different TME types (ORR and PFS; type I: 64%, 14.5 mo; type II: 12%, 2.1 mo; type III: 24%, 3.6 mo; type IV; 41%, 10.8 mo). In patients with PD-L1 High tumors, type I tumors had significantly better ORR and PFS than type III tumors (ORR: p < 0.001 and PFS: p < 0.001). The presence of TP53 and KRAS mutation was related to the density of CD8-positive TILs and PD-L1 expression, respectively.

Differential types of TME, including PD-L1 expression and TIL status, could accurately predict the efficacy of anti-PD-1/PD-L1 therapy.