PD-L1 expression and T cells infiltration in patients with uncommon EGFR-mutant non-small cell lung cancer and the response to immunotherapy

doi:10.1016/j.lungcan.2020.02.010

HFCAS OpenIR

	PD-L1 expression and T cells infiltration in patients with uncommon EGFR-mutant non-small cell lung cancer and the response to immunotherapy
	Chen, Kaiyan 1,2,3; Cheng, Guoping 1,4; Zhang, Fanrong 1,5; Zhu, Guanxia 1,2,3; Xu, Yanjun 1,2,3; Yu, Xiaoqing 1,2,3; Huang, Zhiyu 1,2,3; Fan, Yun 1,2,3
	2020-04-01
发表期刊	LUNG CANCER
ISSN	0169-5002
通讯作者	Fan, Yun(fanyun@zjcc.org.cn)
摘要	Objectives: The efficacy of immunotherapy in epidermal growth factor receptor (EGFR)-activating non-small cell lung cancer (NSCLC) is limited. However, a series of patients with uncommon EGFR alterations was reported to derive clinical benefit from PD-1 blockade. To characterize the tumor immune microenvironment, we retrospectively evaluated tumor PD-L1 expression and T cells infiltration among NSCLC patients with uncommon EGFR mutations. Materials and methods: Immunohistochemistry was used to analyze the expression of PD-L1 and the abundance of CD4+ and CD8+ tumor-infiltrating lymphocytes (TILs). Chi-square test and Cox proportional hazards regression were conducted to investigate the correlations between the immune microenvironment features and clinicopathological variables and survival, as well as to explore the potential of immunotherapy in this patient population. Results: Among 600 NSCLC patients with EGFR alterations, we identified 49 (8.2 %) bearing uncommon mutations, including G719X, L861Q, S768I, and Ex20 ins. In total, 49.0 % (24/49) of these patients showed positive PD-L1 expression in tumor cells, markedly higher than the proportion in patients with classic sensitive mutations (19del and L858R, 12.2 % [67/551], P < 0.05). Furthermore, PD-L1 expression was associated with relatively short overall survival (OS; 15.2 vs 29.3 months, P = 0.006) and was identified as an independent predictor of OS (hazard ratio=2.57, 95 % confidence interval: 1.03-7.12, P = 0.045). Additionally, PD-L1 positivity was predominantly observed among tumors with CD8+ TILs infiltration (P = 0.001). Uncommon EGFR-mutant tumors had a high frequency (36.7 %) of concurrent PD-L1 expression and abundant CD8 + TILs infiltration. Moreover, this dual-positive group exhibited the most unfavorable prognosis (P= 0.023). Notably, patients with PD-L1 and CD8 dual positivity showed a favorable response to PD-1 inhibitors. Conclusions: High rates of concomitant PD-L1 expression and CD8+ TILs within the tumor microenvironment were observed in NSCLC patients with uncommon EGFR mutations. Further investigations are needed to confirm the therapeutic sensitivity to PD-1 blockade in this subgroup.
关键词	Uncommon EGFR Non-small cell lung cancer PD-L1 T cell Immunotherapy
DOI	10.1016/j.lungcan.2020.02.010
关键词[WOS]	TYROSINE KINASE INHIBITORS ; FACTOR RECEPTOR MUTATIONS ; CHECKPOINT INHIBITORS ; NSCLC-PATIENTS ; IMMUNE ESCAPE ; OPEN-LABEL ; BLOCKADE ; SENSITIVITY ; DOCETAXEL ; NIVOLUMAB
收录类别	SCI
语种	英语
资助项目	Basic Public Foundation of Zhejiang Province of China[LGF18H160017]
项目资助者	Basic Public Foundation of Zhejiang Province of China
WOS研究方向	Oncology ; Respiratory System
WOS类目	Oncology ; Respiratory System
WOS记录号	WOS:000526981600015
出版者	ELSEVIER IRELAND LTD
引用统计	被引频次：50[WOS] [WOS记录] [WOS相关记录]
文献类型	期刊论文
条目标识符	http://ir.hfcas.ac.cn:8080/handle/334002/103672
专题	中国科学院合肥物质科学研究院
通讯作者	Fan, Yun
作者单位	1.Chinese Acad Sci, ICBM, Hangzhou 310022, Peoples R China 2.Univ Chinese Acad Sci, Canc Hosp, Dept Med Oncol, Hangzhou 310022, Peoples R China 3.Zhejiang Canc Hosp, Dept Med Oncol, Hangzhou 310022, Peoples R China 4.Zhejiang Canc Hosp, Dept Pathol, Hangzhou 310022, Peoples R China 5.Zhejiang Canc Hosp, Dept Breast Surg, Hangzhou 310022, Peoples R China
推荐引用方式 GB/T 7714	Chen, Kaiyan,Cheng, Guoping,Zhang, Fanrong,et al. PD-L1 expression and T cells infiltration in patients with uncommon EGFR-mutant non-small cell lung cancer and the response to immunotherapy[J]. LUNG CANCER,2020,142.
APA	Chen, Kaiyan.,Cheng, Guoping.,Zhang, Fanrong.,Zhu, Guanxia.,Xu, Yanjun.,...&Fan, Yun.(2020).PD-L1 expression and T cells infiltration in patients with uncommon EGFR-mutant non-small cell lung cancer and the response to immunotherapy.LUNG CANCER,142.
MLA	Chen, Kaiyan,et al."PD-L1 expression and T cells infiltration in patients with uncommon EGFR-mutant non-small cell lung cancer and the response to immunotherapy".LUNG CANCER 142(2020).