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Tumor microenvironm...
Tumor microenvironment evaluation promotes precise checkpoint immunotherapy of advanced gastric cancer
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Zeng, DQ (author)
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Wu, JN (author)
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Luo, HY (author)
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show more...
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Li, Y (author)
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Xiao, J (author)
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Peng, JJ (author)
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Ye, ZL (author)
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Zhou, R (author)
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Yu, YF (author)
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Wang, GF (author)
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Huang, N (author)
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Wu, JH (author)
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Rong, XX (author)
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Sun, L (author)
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Sun, HY (author)
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Qiu, WJ (author)
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Xue, YC (author)
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Bin, JP (author)
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Liao, YL (author)
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- Li, NL (author)
- Karolinska Institutet
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Shi, M (author)
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Kim, KM (author)
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Liao, WJ (author)
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(creator_code:org_t)
- 2021-08-10
- 2021
- English.
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In: Journal for immunotherapy of cancer. - : BMJ. - 2051-1426. ; 9:8
- Related links:
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https://jitc.bmj.com...
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http://kipublication...
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https://doi.org/10.1...
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Abstract
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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.
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- ref (subject category)
- art (subject category)
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- By the author/editor
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Zeng, DQ
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Wu, JN
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Luo, HY
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Li, Y
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Xiao, J
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Peng, JJ
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show more...
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Ye, ZL
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Zhou, R
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Yu, YF
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Wang, GF
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Huang, N
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Wu, JH
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Rong, XX
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Sun, L
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Sun, HY
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Qiu, WJ
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Xue, YC
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Bin, JP
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Liao, YL
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Li, NL
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Shi, M
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Kim, KM
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Liao, WJ
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show less...
- Articles in the publication
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Journal for immu ...
- By the university
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Karolinska Institutet