WFRF:(Zhou YL)
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Tumor microenvironment evaluation promotes precise checkpoint immunotherapy of advanced gastric cancer
- Article/chapterEnglish2021
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- 2021-08-10
- BMJ,2021
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- LIBRIS-ID:oai:prod.swepub.kib.ki.se:150427777
- http://kipublications.ki.se/Default.aspx?queryparsed=id:150427777URI
- https://doi.org/10.1136/jitc-2021-002467DOI
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- Language:English
- Summary in:English
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- Durable 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.
Added entries (persons, corporate bodies, meetings, titles ...)
- Wu, JN (author)
- Luo, HY (author)
- Li, Y (author)
- Xiao, J (author)
- Peng, JJ (author)
- Ye, ZL (author)
- Zhou, R (author)
- Yu, YF (author)
- Wang, GF (author)
- Huang, N (author)
- Wu, JH (author)
- Rong, XX (author)
- Sun, L (author)
- Sun, HY (author)
- Qiu, WJ (author)
- Xue, YC (author)
- Bin, JP (author)
- Liao, YL (author)
- Li, NLKarolinska Institutet (author)
- Shi, M (author)
- Kim, KM (author)
- Liao, WJ (author)
- Karolinska Institutet (creator_code:org_t)
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- In:Journal for immunotherapy of cancer: BMJ9:82051-1426
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