Differential Immune-Related Microenvironment Determines Programmed Cell Death Protein-1/Programmed Death-Ligand 1 Blockade Efficacy in Patients With Advanced NSCLC

被引：43

作者：

Shirasawa, Masayuki ^{[1
]}

Yoshida, Tatsuya ^{[1
,2
]}

Shimoda, Yukiko ^{[1
]}

Md, Daisuke Takayanagi ^{[3
]}

Shiraishi, Kouya ^{[3
]}

Kubo, Takashi ^{[4
]}

Mitani, Sachiyo ^{[4
]}

Md, Yuji Matsumoto ^{[1
]}

Masuda, Ken ^{[1
]}

Md, Yuki Shinno ^{[1
]}

Md, Yusuke Okuma ^{[1
]}

Md, Yasushi Goto ^{[1
]}

Md, Hidehito Horinouchi ^{[1
]}

Ichikawa, Hitoshi ^{[4
]}

Kohno, Takashi ^{[3
]}

Md, Noboru Yamamoto ^{[1
,2
]}

Md, Shingo Matsumoto ^{[5
]}

Md, Koichi Goto ^{[5
]}

Md, Shun-ichi Watanabe ^{[6
]}

Md, Yuichiro Ohe ^{[1
]}

Md, Noriko Motoi ^{[7
]}

机构：

[1] Natl Canc Ctr, Dept Thorac Oncol, Tokyo, Japan

[2] Natl Canc Ctr, Dept Expt Therapeut, Tokyo, Japan

[3] Natl Canc Ctr, Div Genome Biol, Tokyo, Japan

[4] Natl Canc Ctr, Dept Clin Genom, Tokyo, Japan

[5] Natl Canc Ctr Hosp East, Dept Thorac Oncol, Chiba, Japan

[6] Natl Canc Ctr, Dept Thorac Surg, Tokyo, Japan

[7] Natl Canc Ctr, Dept Diagnost Pathol, Tokyo, Japan

来源：

JOURNAL OF THORACIC ONCOLOGY | 2021年 / 16卷 / 12期

关键词：

Non-small lung cell cancer (NSCLC); Anti-PD-1/PD-L1 (programmed death-1/programmed death-ligand 1) antibodies; Tumor microenvironment (TME); The density of CD8-positive tumor-infiltrating lymphocytes (TILs); TUMOR MUTATION BURDEN; LUNG-CANCER; CHECKPOINT INHIBITORS; PD-L1; EXPRESSION; SMALL BIOPSY; SINGLE-ARM; NIVOLUMAB; MULTICENTER; DOCETAXEL; CARCINOMA;

D O I：

10.1016/j.jtho.2021.07.027

中图分类号：

R73 [肿瘤学];

学科分类号：

100214 ;

摘要：

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-L1(High) (tumor proportion score >= 50%)/TILHigh (>85/mm(2); n = 73); type II: PD-L1(Low) (tumor proportion score < 50%)/TILLow (<85/mm(2); n = 70); type III: PDL1(High)/TILLow (n = 37); and type IV: PD-L1(Low)/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-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. Conclusions: Differential types of TME, including PD-L1 expression and TIL status, could accurately predict the efficacy of anti-PD-1/PD-L1 therapy. (C) 2021 International Association for the Study of Lung Cancer. Published by Elsevier Inc. All rights reserved.

引用

页码：2078 / 2090

页数：13

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