Department of Lung Cancer and Immunology, Tongji University Affiliated Shanghai Pulmonary Hospital, Tongji University School of Medicine, Shanghai, China.
Department of Medical Oncology, Tongji University Affiliated Shanghai Pulmonary Hospital, Tongji University School of Medicine, Shanghai, China.
Thorac Cancer. 2020 Aug;11(8):2130-2136. doi: 10.1111/1759-7714.13504. Epub 2020 Jun 4.
The abundance of tumor infiltrating CD8 T cells is an important parameter for antitumor effect of PD-1/PD-L1 immune checkpoint inhibitors, which is less in epidermal growth factor receptor (EGFR) mutation than wild-type non-small cell lung cancer (NSCLC). The mechanism still requires further study.
In total 190 surgical lung adenocarcinoma samples were included. EGFR mutation was detected using amplification-refractory mutation system. CD8 T cells and apoptosis were assessed by immunohistochemistry and immunofluorescence staining in tumor samples. Exosomes extracted from lung cancer cell lines with and without EGFR mutation were used to test the function of promoting apoptosis in vitro.
The ratio of CD8 tumor infiltration lymphocytes was significantly lower in EGFR-mutant than in wild-type patients (P = 0.026). A higher ratio of apoptosis was also prone to occur in EGFR-mutant patients (P = 0.035). The distribution of apoptosis was not statistically associated with the ratio of CD8 TILs. An in vitro experiment indicated that exosomes secreted by EGFR-mutant non-small cell lung cancer cell lines PC9 and HCC827 were more capable of promoting CD8 T cell apoptosis than EGFR wild-type cell lines H1299 and SK-MES-1 (P = 0.007 and P = 0.010, respectively).
Non-small cell lung cancer EGFR mutation could promote CD8 T cell apoptosis more than wild-type. Inhibiting CD8 + TILs apoptosis may strengthen immunotherapy effects in EGFR-mutant NSCLC patients.
肿瘤浸润 CD8 T 细胞的丰度是 PD-1/PD-L1 免疫检查点抑制剂抗肿瘤效应的一个重要参数，在表皮生长因子受体（EGFR）突变型非小细胞肺癌（NSCLC）中比野生型少。其机制仍需进一步研究。
共纳入 190 例手术肺腺癌样本。采用扩增受阻突变系统检测 EGFR 突变。通过免疫组化和免疫荧光染色检测肿瘤样本中 CD8 T 细胞和细胞凋亡。用有无 EGFR 突变的肺癌细胞系提取的外泌体进行体外促进细胞凋亡的功能测试。
EGFR 突变型患者的 CD8 肿瘤浸润淋巴细胞比例明显低于野生型患者（P = 0.026）。EGFR 突变型患者也更容易发生较高比例的细胞凋亡（P = 0.035）。细胞凋亡的分布与 CD8 TIL 比例无统计学关联。体外实验表明，EGFR 突变型非小细胞肺癌细胞系 PC9 和 HCC827 分泌的外泌体比 EGFR 野生型细胞系 H1299 和 SK-MES-1 更能促进 CD8 T 细胞凋亡（P = 0.007 和 P = 0.010）。
非小细胞肺癌 EGFR 突变比野生型更能促进 CD8 T 细胞凋亡。抑制 CD8+TILs 凋亡可能会增强 EGFR 突变型 NSCLC 患者的免疫治疗效果。
