Tumor microenvironment evaluation promotes precise checkpoint immunotherapy of advanced gastric cancer
| Autor: | Na Huang, Jianjun Peng, Jiani Wu, Nailin Li, Li Sun, Zilan Ye, Huiying Sun, Yunfang Yu, Jianhua Wu, Jianping Bin, Yong Li, Min Shi, Kyoung-Mee Kim, Xiaoxiang Rong, Jian Xiao, Wangjun Liao, Wenjun Qiu, Rui Zhou, Yulin Liao, Dongqiang Zeng, Gaofeng Wang, Huiyan Luo, Yichen Xue |
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| Jazyk: | angličtina |
| Rok vydání: | 2021 |
| Předmět: |
Oncology
Adult Male Cancer Research medicine.medical_specialty medicine.medical_treatment Immunology Phases of clinical research Pembrolizumab gastrointestinal neoplasms Stomach Neoplasms Internal medicine Immunotherapy Biomarkers medicine Tumor Microenvironment Immunology and Allergy Humans Prospective Studies Immune Checkpoint Inhibitors RC254-282 Aged Pharmacology Tumor microenvironment business.industry Area under the curve Microsatellite instability Computational Biology Neoplasms. Tumors. Oncology. Including cancer and carcinogens Immunotherapy Middle Aged medicine.disease Immune checkpoint Molecular Medicine Biomarker (medicine) Female business |
| Zdroj: | Journal for ImmunoTherapy of Cancer, Vol 9, Iss 8 (2021) Journal for Immunotherapy of Cancer |
| ISSN: | 2051-1426 |
| Popis: | BackgroundDurable efficacy of immune checkpoint blockade (ICB) occurred in a small number of patients with metastatic gastric cancer (mGC) and the determinant biomarker of response to ICB remains unclear.MethodsWe developed an open-source TMEscore R package, to quantify the tumor microenvironment (TME) to aid in addressing this dilemma. Two advanced gastric cancer cohorts (RNAseq, N=45 and NanoString, N=48) and other advanced cancer (N=534) treated with ICB were leveraged to investigate the predictive value of TMEscore. Simultaneously, multi-omics data from The Cancer Genome Atlas of Stomach Adenocarcinoma (TCGA-STAD) and Asian Cancer Research Group (ACRG) were interrogated for underlying mechanisms.ResultsThe predictive capacity of TMEscore was corroborated in patient with mGC cohorts treated with pembrolizumab in a prospective phase 2 clinical trial (NCT02589496, N=45, area under the curve (AUC)=0.891). Notably, TMEscore, which has a larger AUC than programmed death-ligand 1 combined positive score, tumor mutation burden, microsatellite instability, and Epstein-Barr virus, was also validated in the multicenter advanced gastric cancer cohort using NanoString technology (N=48, AUC=0.877). Exploration of the intrinsic mechanisms of TMEscore with TCGA and ACRG multi-omics data identified TME pertinent mechanisms including mutations, metabolism pathways, and epigenetic features.ConclusionsCurrent study highlighted the promising predictive value of TMEscore for patients with mGC. Exploration of TME in multi-omics gastric cancer data may provide the impetus for precision immunotherapy. |
| Databáze: | OpenAIRE |
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