ArticleJournal for immunotherapy of cancer2020
Distinctive germline expression of class I human leukocyte antigen (HLA) alleles and DRB1 heterozygosis predict the outcome of patients with non-small cell lung cancer receiving PD-1/PD-L1 immune checkpoint blockade.
Article in Journal for immunotherapy of cancer, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 36 papers.
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Who cites it
36 citing papers in PubMed, 44 citations in OpenAlex.
- Neoadjuvant mFOLFOX6 plus camrelizumab and apatinib in colon cancer and biomarker research via spatiotemporal-omics profiling.NPJ precision oncology · 2026Article
- Patient-specific HLA-I subtypes predict response to immune checkpoint blockade.Oncoimmunology · 2025Article
- Risk factors and mechanisms of immune checkpoint inhibitor-related pneumonitis.Human vaccines & immunotherapeutics · 2025Review
- Risk factors and mechanisms of immune checkpoint inhibitor-related pneumonitis.Human vaccines & immunotherapeutics · 2025Review
- Association of HLA-A*02:01 type with efficacy and toxicity of immune checkpoint inhibitor therapy in melanoma patients: a retrospective cohort study.BMC cancer · 2025Article
- A rapid ecologic analysis, confirmed by a case-control study, identifies class I HLA alleles correlated to the risk of COVID-19.Journal of translational medicine · 2025Article
- The epidemiology, etiology, and future prophylactic options for cancers in Mainland China.Frontiers in oncology · 2025Review
- Germline Human Leukocyte Antigen Status is Associated With Immunotherapy-Induced Pneumonitis and Treatment Response in Patients With Non-Small Cell Lung Cancer With High Programmed Death-Ligand 1 Expression.JTO clinical and research reports · 2025Article
- Advances in the mechanisms, imaging characteristics and management strategies for immune checkpoint inhibitor-related pneumonitis.Frontiers in immunology · 2025Review
- Prognostic significance of B cell senescence-associated genes as risk markers in prostate adenocarcinoma.Translational cancer research · 2024Article
- Review
- Effect of HLA Genotype on Anti-PD-1 Antibody Treatment for Advanced Renal Cell Carcinoma in the SNiP-RCC Study.Journal of immunology (Baltimore, Md. : 1950) · 2024Article
- CXCR6-positive circulating mucosal-associated invariant T cells can identify patients with non-small cell lung cancer responding to anti-PD-1 immunotherapy.Journal of experimental & clinical cancer research : CR · 2024Article
- Class II HLA-DRB4 is a predictive biomarker for survival following immunotherapy in metastatic non-small cell lung cancer.Scientific reports · 2024Article
- Article
- CARdioimaging in Lung Cancer PatiEnts Undergoing Radical RadioTherapy: CARE-RT Trial.Diagnostics (Basel, Switzerland) · 2023Article
- Mechanisms of drug resistance to immune checkpoint inhibitors in non-small cell lung cancer.Frontiers in immunology · 2023Review
- Impact of germline HLA genotypes on clinical outcomes in patients with urothelial cancer treated with pembrolizumab.Cancer science · 2022Article
- Effect of HLA genotype on intravesical recurrence after bacillus Calmette-Guérin therapy for non-muscle-invasive bladder cancer.Cancer immunology, immunotherapy : CII · 2022Article
- PD-1/PD-L1 immune-checkpoint blockade induces immune effector cell modulation in metastatic non-small cell lung cancer patients: A single-cell flow cytometry approach.Frontiers in oncology · 2022Article
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Authors and funding
26 authors at 9 institutions in 3 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundNivolumab is a human monoclonal antibody against programmed cell death receptor-1 (PD-1) able to rescue quiescent tumor infiltrating cytotoxic T lymphocytes (CTLs) restoring their ability to kill target cells expressing specific tumor antigen-derived epitope peptides bound to homologue human leukocyte antigen (HLA) molecules. Nivolumab is currently an active but expensive therapeutic agent for metastatic non-small cell lung cancer (mNSCLC), producing, in some cases, immune-related adverse events (irAEs). At the present, no reliable biomarkers have been validated to predict either treatment response or adverse events in treated patients.
methodsWe performed a retrospective multi-institutional analysis including 119 patients with mNSCLC who received PD-1 blockade since November 2015 to investigate the predictive role of germinal class I HLA and DRB1 genotype. We investigated the correlation among patients' outcome and irAEs frequency with specific HLA A, B, C and DRB1 alleles by reverse sequence-specific oligonucleotide (SSO) DNA typing.
resultsA poor outcome in patients negative for the expression of two most frequent HLA-A alleles was detected (HLA: HLA-A*01 and or A*02; progression-free survival (PFS): 7.5 (2.8 to 12.2) vs 15.9 (0 to 39.2) months, p=0.01). In particular, HLA-A*01-positive patients showed a prolonged PFS of 22.6 (10.2 to 35.0) and overall survival (OS) of 30.8 (7.7 to 53.9) months, respectively. We also reported that HLA-A and DRB1 locus heterozygosis (het) were correlated to a worse OS if we considered het in the locus A; in reverse, long survival was correlated to het in DRB1.
conclusionsThis study demonstrate that class I and II HLA allele characterization to define tumor immunogenicity has relevant implications in predicting nivolumab efficacy in mNSCLC and provide the rationale for further prospective trials of cancer immunotherapy.
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