Differential Immune-Related Microenvironment Determines Programmed Cell Death Protein-1/Programmed Death-Ligand 1 Blockade Efficacy in Patients With Advanced NSCLC.
J Thorac Oncol
; 16(12): 2078-2090, 2021 12.
Article
en En
| MEDLINE
| ID: mdl-34419685
ABSTRACT
INTRODUCTION:
Programmed death-ligand 1 (PD-L1) expression is not a completely reliable predictive marker of the efficacy of anti-programmed cell death protein-1 (PD-1)/PD-L1 therapy in patients with advanced NSCLC. Immune-related tumor microenvironment (TME) is classified into four different types based on the tumor-infiltrating lymphocyte (TIL) status and PD-L1 expression.METHODS:
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.RESULTS:
Overall, 228 patients were included in the analysis. The patients were classified into the following four groups type I PD-L1High (tumor proportion score ≥ 50%)/TILHigh (≥85/mm2; n = 73); type II PD-L1Low (tumor proportion score < 50%)/TILLow (<85/mm2; n = 70); type III PD-L1High/TILLow (n = 37); and type IV PD-L1Low/TILHigh (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-L1High 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.CONCLUSIONS:
Differential types of TME, including PD-L1 expression and TIL status, could accurately predict the efficacy of anti-PD-1/PD-L1 therapy.Palabras clave
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Carcinoma de Pulmón de Células no Pequeñas
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Antígeno B7-H1
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Inhibidores de Puntos de Control Inmunológico
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Neoplasias Pulmonares
Tipo de estudio:
Observational_studies
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Prognostic_studies
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Risk_factors_studies
Límite:
Humans
Idioma:
En
Revista:
J Thorac Oncol
Año:
2021
Tipo del documento:
Article
País de afiliación:
Japón