Association of CD8 T cell apoptosis and EGFR mutation in non-small lung cancer patients

Lung Cancer

Zhao C, et al. Thorac Cancer 2020.


BACKGROUND: 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.

METHODS: 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.

RESULTS: 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).

CONCLUSIONS: 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.