Association of CD8 T cell apoptosis and EGFR mutation in non-small lung cancer patients
Chao Zhao1, Chunxia Su2, Xuefei Li1
1Department of Lung Cancer and Immunology, Tongji University Affiliated Shanghai Pulmonary Hospital, Tongji University School of Medicine, Shanghai, China.
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.
Insights
Epidermal growth factor receptor (EGFR) mutations in non-small cell lung cancer (NSCLC) promote CD8 T cell apoptosis. Inhibiting this apoptosis may enhance immunotherapy efficacy in EGFR-mutant NSCLC patients.
Area of Science:
- Oncology
- Immunology
- Molecular Biology
Background:
- Tumor-infiltrating CD8 T cells are crucial for PD-1/PD-L1 inhibitor efficacy.
- CD8 T cell abundance is lower in EGFR-mutant non-small cell lung cancer (NSCLC) compared to wild-type.
- The underlying mechanisms require further investigation.
Purpose of the Study:
- To investigate the impact of epidermal growth factor receptor (EGFR) mutations on CD8 T cell infiltration and apoptosis in NSCLC.
- To explore the role of exosomes in mediating CD8 T cell apoptosis in EGFR-mutant NSCLC.
Main Methods:
- Analysis of 190 lung adenocarcinoma samples for EGFR mutation status, CD8 T cell infiltration, and apoptosis.
- Immunohistochemistry and immunofluorescence staining were employed.
- In vitro experiments using exosomes from EGFR-mutant and wild-type NSCLC cell lines.
Main Results:
- EGFR-mutant NSCLC showed significantly lower CD8 T cell infiltration (P = 0.026) and higher apoptosis rates (P = 0.035).
- Exosomes from EGFR-mutant NSCLC cell lines promoted CD8 T cell apoptosis more effectively than those from wild-type cell lines (P = 0.007, P = 0.010).
Conclusions:
- EGFR mutations in NSCLC can enhance CD8 T cell apoptosis.
- Targeting CD8+ T cell apoptosis inhibition may improve immunotherapy outcomes for EGFR-mutant NSCLC patients.
More Related Videos
Related Concept Videos
02:38Mitogens and the Cell Cycle
01:17The Extrinsic Apoptotic Pathway
02:57Targeted Cancer Therapies
There are several types of targeted therapies against...