PD-L1 expression, tumor mutational burden, and immune cell infiltration in non-small cell lung cancer patients with
Tiantian Ma1, Jin Jiao1, Ran Huo1
1Department of Medical Oncology, Affiliated Hospital of Hebei University, Hebei Key Laboratory of Cancer Radiotherapy and Chemotherapy, Baoding, China.
Background:
Immunotherapy using programmed cell death protein 1/programmed death-ligand 1 (PD-1/PD-L1) inhibitors seems less effective in non-small cell lung cancer (NSCLC) patients with epithelial growth factor receptor (EGFR) mutations. Varied responses to PD-1/PD-L1 inhibitors have recently been observed in NSCLC patients harboring different types of EGFR mutations. Some EGFR-mutated NSCLC patients may benefit from PD-1/PD-L1 inhibitors. At present, PD-L1 expression, tumor mutational burden (TMB), and tumor immune microenvironment (TIME) are biomarkers for predicting the efficacy of PD-1/PD-L1 inhibitors in NSCLC patients. We retrospectively evaluated PD-L1 expression, TMB, and immune cell infiltration in NSCLC patients with EGFR mutation subtypes.
Methods:
PD-L1 expression, TMB, and the abundance of immune cell infiltration in NSCLC patients were evaluated in public databases and clinical samples. TMB was detected using the NGS technique, PD-L1 was detected using immunohistochemistry, and the abundance of immune cell infiltration in NSCLC samples was detected using multiple immunohistochemistry.
Results:
PD-L1 expression and TMB were lower in EGFR-mutated NSCLCs than in wild-type patients. Differences in the abundance of immune cell infiltration were also observed between EGFR-mutated and wild-type NSCLC. The expression of PD-L1, TMB, and abundance of immune cell infiltration were different in patients harboring different subtypes of EGFR mutations. Patients with uncommon EGFR mutations, especially the G719X mutation, showed higher TMB and expressions of PD-L1 than classical EGFR mutations. M1 macrophages were higher in uncommon EGFR mutations than classical EGFR mutations.
Conclusions:
The expression of PD-L1 and TMB in uncommon EGFR-mutated NSCLCs, especially the G719X mutation, were higher than those for classical EGFR-mutated NSCLCs and similar to EGFR wild-type. The abundance of immune cell infiltration in uncommon EGFR-mutated NSCLCs was similar to that in EGFR wild-type. Our findings suggest that uncommon EGFR-mutated NSCLCs may benefit from PD-1/PD-L1 inhibitors.
Insights
Uncommon EGFR mutations in non-small cell lung cancer (NSCLC) show higher PD-L1 expression and tumor mutational burden (TMB), suggesting potential benefit from PD-1/PD-L1 inhibitors. These biomarkers may help predict immunotherapy response in specific NSCLC patient groups.
Area of Science:
- Oncology
- Immunology
- Genetics
Background:
- Immunotherapy with PD-1/PD-L1 inhibitors shows varied efficacy in non-small cell lung cancer (NSCLC) patients with EGFR mutations.
- Biomarkers like PD-L1 expression, tumor mutational burden (TMB), and tumor immune microenvironment (TIME) are crucial for predicting treatment response.
- Understanding differences among EGFR mutation subtypes is key to optimizing immunotherapy for NSCLC.
Purpose of the Study:
- To investigate PD-L1 expression, TMB, and immune cell infiltration across different EGFR mutation subtypes in NSCLC.
- To identify potential biomarkers that predict response to PD-1/PD-L1 inhibitors in EGFR-mutated NSCLC.
- To compare these biomarkers between uncommon and classical EGFR mutations, as well as wild-type NSCLC.
Main Methods:
- Retrospective analysis of PD-L1 expression, TMB, and immune cell infiltration in NSCLC patients with EGFR mutations.
- Utilized public databases and clinical samples for evaluation.
- Assessed TMB via next-generation sequencing (NGS), PD-L1 via immunohistochemistry, and immune cell infiltration via multiple immunohistochemistry.
Main Results:
- EGFR-mutated NSCLCs exhibited lower PD-L1 expression and TMB compared to wild-type.
- Significant differences in immune cell infiltration were observed between EGFR-mutated and wild-type NSCLC.
- Uncommon EGFR mutations (e.g., G719X) showed higher TMB and PD-L1 expression than classical mutations, with increased M1 macrophage abundance.
Conclusions:
- Uncommon EGFR-mutated NSCLCs, particularly those with G719X, demonstrated higher PD-L1 and TMB levels, comparable to wild-type NSCLC.
- Immune cell infiltration in uncommon EGFR-mutated NSCLC was similar to wild-type.
- These findings suggest that NSCLC patients with uncommon EGFR mutations may benefit from PD-1/PD-L1 inhibitor therapy.
