Copy number loss in granzyme genes confers resistance to immune checkpoint inhibitor in nasopharyngeal carcinoma

Autor: Yunpeng Yang, Yang Zhang, Hua Bao, Xue Wu, Wanxiangfu Tang, Shaodong Hong, Wenfeng Fang, Ao Wang, Yang Shao, Li Zhang, Yan Huang, Qingguang Lin, Yuxiang Ma, Hongyun Zhao, Xi Chen
Jazyk: angličtina
Rok vydání: 2021
Předmět:
0301 basic medicine
Oncology
Male
Cancer Research
Time Factors
medicine.medical_treatment
Programmed Cell Death 1 Receptor
Gene Dosage
Granzymes
Metastasis
0302 clinical medicine
Immunotherapy Biomarkers
Immunology and Allergy
Immune Checkpoint Inhibitors
RC254-282
Nasopharyngeal Carcinoma
biology
Neoplasms. Tumors. Oncology. Including cancer and carcinogens
Middle Aged
Progression-Free Survival
030220 oncology & carcinogenesis
Disease Progression
Molecular Medicine
Female
immunotherapy
Adult
medicine.medical_specialty
DNA Copy Number Variations
Immunology
Antibodies
Monoclonal
Humanized
GZMB
03 medical and health sciences
Young Adult
Clinical Trials
Phase II as Topic
head and neck neoplasms
Internal medicine
medicine
Biomarkers
Tumor
Humans
Aged
Retrospective Studies
Pharmacology
Chemotherapy
business.industry
Nasopharyngeal Neoplasms
Immunotherapy
medicine.disease
Granzyme B
030104 developmental biology
Granzyme
Nasopharyngeal carcinoma
Drug Resistance
Neoplasm
tumor biomarkers
biology.protein
business
Granzyme H
Zdroj: Journal for ImmunoTherapy of Cancer, Vol 9, Iss 3 (2021)
Journal for Immunotherapy of Cancer
ISSN: 2051-1426
Popis: BackgroundAnti-programmed death (PD)-1 therapy has recently been used in recurrent or metastatic (R/M) nasopharyngeal carcinoma (NPC). The long-term survival and its biomarkers responding to anti-PD-1 treatment in patients with R/M NPC remain unclear.MethodsPatients with R/M NPC were enrolled between March 2016 and January 2018 from two phase I clinical trials. The median follow-up period was 24.7 months. Eligible patients progressed on standard chemotherapy had measurable disease by Response Evaluation Criteria in Solid Tumor V.1.1. Non-obligatory contemporaneous tumor samples were collected for whole-exome sequencing. The primary outcome was objective response rate (ORR). Duration of response (DOR), progression-free survival (PFS), and overall survival (OS) were secondary outcomes assessed in all patients.ResultsAmong 124 evaluable patients, anti-PD-1 therapy achieved an ORR of 29.8% and a durable clinical benefit rate of 60.5%. The median OS (mOS) was 17.1 months (95% CI 14.2 to 24.7), median PFS (mPFS) was 3.8 months (95% CI 3.4 to 6.0), and median DOR was 9.5 months. Significant OS benefit from treatment was observed in patients without liver metastasis (23.8 vs 13.3 months, p=0.006). Copy number deletion in genes encoding granzyme B or granzyme H (GZMB/H) was associated with poor treatment outcome (mPFS altered vs wildtype: 1.7 vs 3.6 months, p=0.03; mOS altered vs wildtype: 10.1 vs 18 months, p=0.012).ConclusionsAnti-PD-1 treatment provided promising clinical benefit in pretreated patients with R/M NPC. Copy number loss in either GZMB or GZMH genes was associated with reduced survival.
Databáze: OpenAIRE
Externí odkaz: