ArticleScientific reports2024
Class II HLA-DRB4 is a predictive biomarker for survival following immunotherapy in metastatic non-small cell lung cancer.
Article in Scientific reports, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 15 papers.
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15 citing papers in PubMed, 14 citations in OpenAlex.
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- Lung cancer vaccines to enhance immune checkpoint inhibitor therapy: evidence and future perspectives.Journal of hematology & oncology · 2026Review
- Association between HLA-DRB1*04:05 and the efficacy of immune checkpoint inhibitors for patients with advanced cancer.Frontiers in endocrinology · 2026Article
- Immune checkpoint inhibitor therapy for gastric cancer: current status, therapeutic challenges, and future prospects.Frontiers in immunology · 2026Review
- Enhanced immunotherapy response in lung adenocarcinoma patients with COPD: insights into tumor cells and immune microenvironment characteristics.Cell communication and signaling : CCS · 2025Article
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- The origin of autoimmune diseases: is there a role for ancestral HLA-II haplotypes in immune hyperactivity.Frontiers in immunology · 2025Review
- Imaging antigen processing and presentation in cancer.Immunotherapy advances · 2025Review
- Predictive Biomarkers and Resistance Mechanisms of Checkpoint Inhibitors in Malignant Solid Tumors.International journal of molecular sciences · 2024Review
- Advances and prospects of biomarkers for immune checkpoint inhibitors.Cell reports. Medicine · 2024Review
- Immune-related adverse events of antibody-based biological medicines in cancer therapy.Journal of cellular and molecular medicine · 2024Review
- Development of pituitary dysfunction and destructive thyroiditis is associated with better survival in non-small cell lung cancer patients treated with programmed cell death-1 inhibitors: a prospective study with immortal time bias correction.Frontiers in endocrinology · 2024Article
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Authors and funding
10 authors at 3 institutions in 1 country.
Funding
Abstract
Immune checkpoint inhibitors (ICI) are important treatment options for metastatic non-small cell lung cancer (mNSCLC). However, not all patients benefit from ICIs and can experience immune-related adverse events (irAEs). Limited understanding exists for germline determinants of ICI efficacy and toxicity, but Human Leukocyte Antigen (HLA) genes have emerged as a potential predictive biomarker. We performed HLA typing on 85 patients with mNSCLC, on ICI therapy and analyzed the impact of HLA Class II genotype on progression free survival (PFS), overall survival (OS), and irAEs. Most patients received pembrolizumab (83.5%). HLA-DRB4 genotype was seen in 34/85 (40%) and its presence correlated with improved OS in both univariate (p = 0.022; 26.3 months vs 10.2 months) and multivariate analysis (p = 0.011, HR 0.49, 95% CI [0.29, 0.85]). PFS did not reach significance (univariate, p = 0.12, 8.2 months vs 5.1 months). Eleven patients developed endocrine irAEs. HLA-DRB4 was the predominant genotype among these patients (9/11, 81.8%). Cumulative incidence of endocrine irAEs was higher in patients with HLA-DRB4 (p = 0.0139). Our study is the first to suggest that patients with metastatic NSCLC patients on ICI therapy with HLA-DRB4 genotype experience improved survival outcomes. Patients with HLA-DRB4 had the longest median OS (26.3 months). Additionally, we found a correlation between HLA-DRB4 and the occurrence of endocrine irAEs.
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