1. Association of PTPRT mutations with immune checkpoint inhibitors response and outcome in melanoma and non‐small cell lung cancer
- Author
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Wenjing Zhang, Qinghua Wang, Yuting Li, Chao Sheng, Fuyan Shi, Suzhen Wang, and Yujia Kong
- Subjects
Oncology ,Cancer Research ,medicine.medical_specialty ,Lung Neoplasms ,medicine.medical_treatment ,NSCLC ,medicine.disease_cause ,Immune system ,Germline mutation ,Carcinoma, Non-Small-Cell Lung ,Internal medicine ,Biomarkers, Tumor ,Humans ,Medicine ,Radiology, Nuclear Medicine and imaging ,Lung cancer ,Immune Checkpoint Inhibitors ,Melanoma ,PTPRT ,RC254-282 ,Mutation ,business.industry ,PTPRT mutation ,Receptor-Like Protein Tyrosine Phosphatases, Class 2 ,Neoplasms. Tumors. Oncology. Including cancer and carcinogens ,Immunotherapy ,medicine.disease ,Phosphoric Monoester Hydrolases ,biomarker ,Biomarker (medicine) ,immunotherapy ,business - Abstract
Purpose Protein tyrosine phosphatase receptor type T (PTPRT), which is a well‐known phosphatase and mutates frequently in melanoma and non‐small cell lung cancer (NSCLC). Our research aims to elucidate its mutation association with immune checkpoint inhibitors (ICI) efficacy. Methods We integrated whole‐exome sequencing (WES)‐based somatic mutation profiles and clinical characteristics of 631 melanoma samples received ICI agents from eight studies and 109 NSCLC samples from two studies. For validation, 321 melanoma and 350 NSCLC immunotherapy samples with targeted next‐generation sequencing (NGS) were employed. Besides, an independent NSCLC cohort contained 240 samples was also collected for further corroboration. Distinct immune infiltration was evaluated according to the PTPRT mutational status. Results In the WES melanoma cohort, patients with PTPRT mutations harbored a significantly elevated ICI response rate (40.5% vs. 28.6%, p = 0.036) and a prolonged survival outcome (35.3 vs. 24.9 months, p = 0.006). In the WES NSCLC cohort, the favorable response and immunotherapy survival were also observed in PTPRT‐mutated patients (p = 0.036 and 0.019, respectively). For the validation cohorts, the associations of PTRPT mutations with better prognoses were identified in melanoma, NSCLC, and pan‐cancer patients with targeted‐NGS (all p
- Published
- 2021