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

	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 2,3,4; Cheng, Guoping 2,5; Zhang, Fanrong 1,2; Zhu, Guanxia 2,3,4; Xu, Yanjun 2,3,4; Yu, Xiaoqing 2,3,4; Huang, Zhiyu 2,3,4; Fan, Yun 2,3,4
刊名	LUNG CANCER
	2020-04-01
卷号	142
关键词	Uncommon EGFR Non-small cell lung cancer PD-L1 T cell Immunotherapy
ISSN号	0169-5002
DOI	10.1016/j.lungcan.2020.02.010
通讯作者	Fan, Yun(fanyun@zjcc.org.cn)
英文摘要	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.
资助项目	Basic Public Foundation of Zhejiang Province of China[LGF18H160017]
WOS关键词	TYROSINE KINASE INHIBITORS ; FACTOR RECEPTOR MUTATIONS ; CHECKPOINT INHIBITORS ; NSCLC-PATIENTS ; IMMUNE ESCAPE ; OPEN-LABEL ; BLOCKADE ; SENSITIVITY ; DOCETAXEL ; NIVOLUMAB
WOS研究方向	Oncology ; Respiratory System
语种	英语
出版者	ELSEVIER IRELAND LTD
WOS记录号	WOS:000526981600015
资助机构	Basic Public Foundation of Zhejiang Province of China
内容类型	期刊论文
源URL	[http://ir.hfcas.ac.cn:8080/handle/334002/103671]
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.Zhejiang Canc Hosp, Dept Breast Surg, Hangzhou 310022, Peoples R China 2.Chinese Acad Sci, ICBM, Hangzhou 310022, Peoples R China 3.Univ Chinese Acad Sci, Canc Hosp, Dept Med Oncol, Hangzhou 310022, Peoples R China 4.Zhejiang Canc Hosp, Dept Med Oncol, Hangzhou 310022, Peoples R China 5.Zhejiang Canc Hosp, Dept Pathol, 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).