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Published on: September 13, 2018
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The association of genomic alterations with PD-L1 expression in Chinese patients with EGFR/ALK wild-type lung
Fangfang Liu1, Xuemei Zhang1, Mengyao Lu1
1Department of Oncology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
Cancer Medicine
|February 24, 2024
Summary
High tumor mutational burden and specific gene alterations correlate with PD-L1 positivity in lung adenocarcinoma. Hippo pathway alterations are linked to better immunotherapy outcomes in these patients.
Area of Science:
- Oncology
- Immunotherapy
- Genomics
Background:
- Programmed death-ligand 1 (PD-L1) expression is a key biomarker for predicting immune checkpoint inhibitor (ICI) response in non-small cell lung cancer (NSCLC) patients without EGFR/ALK mutations.
- Understanding the molecular and immune microenvironment characteristics associated with PD-L1 expression is crucial for optimizing ICI therapy in this patient population.
Purpose of the Study:
- To investigate the clinical, molecular, and immune microenvironment features associated with PD-L1 expression in Chinese patients with EGFR/ALK wild-type lung adenocarcinoma.
- To explore the relationship between genomic alterations and immunotherapy outcomes in this specific patient group.
Main Methods:
- Retrospective analysis of tumor samples from 359 Chinese patients with EGFR/ALK wild-type lung adenocarcinoma.
- Comprehensive evaluation of PD-L1 expression (tumor proportion score, TPS ≥ 1% vs. < 1%) and next-generation sequencing (NGS)-targeted sequencing.
- Comparison of clinical characteristics, gene mutations, pathways, and immune signatures between PD-L1 positive and negative groups.
Main Results:
- High tumor mutational burden was significantly associated with PD-L1 positivity.
- TP53, KRAS, and other gene alterations were more frequent in PD-L1 positive patients.
- The Hippo pathway showed higher alteration frequencies in PD-L1 positive patients and was linked to improved immunotherapy outcomes, with associated increases in CD68+ PD-L1+ macrophages and CD8+ T cells.
Conclusions:
- Genomic features associated with PD-L1 expression in Chinese EGFR/ALK wild-type lung adenocarcinoma patients provide insights into immunotherapy response.
- Hippo pathway alterations represent a potential predictive biomarker for improved immunotherapy outcomes.
- Further clinical and functional studies are warranted to elucidate the link between the Hippo pathway, PD-L1 expression, and immunotherapy efficacy.
