非小细胞肺癌组织免疫微环境的特点及其临床意义

Charaoteristics and clinical significance of immune microenvironment in non-small cell lung cancer tissues

目的:探讨基于非小细胞肺癌(non-small cell lung cancer,NSCLC)患者原发灶组织中程序性死亡受体-配体1(programmed death-ligand 1,PD-L1)表达和间质中CD8^+T细胞浸润的免疫微环境分型的特点及其临床意义。方法:回顾性分析2016年1月到2018年7月空军特色医学中心收治的74例NSCLC患者的石蜡组织标本及临床病理资料,所有患者均有EGFR基因检测结果、未接受放化疗及靶向治疗。采用免疫组化方法检测组织中PD-L1表达及间质中CD8^+T细胞浸润,分别分析PD-L1、CD8^+T细胞及基于两者的免疫微环境分型与病理参数和患者生存的关系。结果:NSCLC患者原发灶组织中PD-L1表达在不同性别、病理类型、吸烟史、EFGR突变组中有明显差异(均P<0.05),CD8^+T细胞浸润在不同TNM分期、淋巴结转移组织各组中有明显差异(均P<0.05);PD-L1表达与EGFR突变显著相关(P=0.000),而CD8^+T细胞浸润与EGFR突变不相关(P=0.605)。EGFR野生型患者免疫微环境以CD8^+PD-L1+(Ⅰ型)为主、突变型以CD8-PD-L1-(Ⅱ型)及CD8^+PD-L1-(Ⅳ型)为主。免疫微环境分型在不同EGFR突变、吸烟史、病理分化程度的各组中分布有明显差异(均P<0.05),且与EGFR突变显著相关(P<0.05)。随访显示处于无病生存期、复发转移和死亡患者中分别以Ⅰ型、Ⅱ型和Ⅰ型最多。结论:本组NSCLC患者肿瘤免疫微环境分型分布主要以Ⅰ型最多、Ⅲ型最少,其分型与EGFR突变、吸烟史及病理分化有关;EGFR突变患者以CD8^+PD-L1-(Ⅱ)型和CD8^+PD-L1-(Ⅳ型)为主,且与PD-L1低表达相关。

Objective: To investigate the characteristics and clinical significance of the immunomicroenvironment typing based on the expression of programmed death-ligand 1(PD-L1) and the infiltration of CD8^+T cells in the stroma in patients with non-small cell lung cancer(NSCLC). Methods: Paraffin tissue specimens and relevant clinicopathological data of 74 NSCLC patients admitted to our hospital from January 2016 to July 2018 were collected. All patients received EGFR gene test, and none received radiotherapy, chemotherapy or targeted therapy. Immunohistochemistry was used to detect the expression of PD-L1 in tissues and the infiltration of CD8^+T cells in interstitium, and the relationship between PD-L1, CD8^+T cells, and the immune microenvironment typing based on both, and the pathological parameters and the survival of patients was analyzed. Results: PD-L1 expression in the primary tumor of NSCLC patients showed statistical differences in gender, pathological type, smoking history, EFGR gene mutation status(P<0.05). The infiltration of CD8^+T lymphocytes in tumor microenvironment showed statistically significant differences in different TNM stage and lymph node metastasis(P<0.05), PD-L1 expression was significantly correlated with EGFR mutation(P=0.000), while CD8^+T lymphocyte infiltration was not correlated with EGFR mutation(P=0.605). The immunomicroenvironment of EGFR wild-type patients was mainly(CD8^+PD-L1^+)(type Ⅰ), and the mutants were mainly(CD8-PD-L1-)(type Ⅱ) and(CD8^+PD-L1-)(type IV). The distribution of immune microenvironmental typing in each group with different EGFR mutation, smoking history and pathological differentiation degree was significantly different(P<0.05) and significantly correlated with EGFR mutation(P<0.05). Follow-up showed that the patients with disease-free survival, recurrence and metastasis and death were the most in type Ⅰ, type Ⅱ and type Ⅰ, respectively. Conclusions: In this study,the distribution of tumor immunomicroenvironmental typing in NSCLC patients was mainly the highest in type I and the lowest in type Ⅲ, which was related to EGFR mutation, smoking history and pathological differentiation. Patients with EGFR mutations were mainly of type Ⅱ and type Ⅳ, and were associated with low expression of PD-L1.