Pan-cancer adaptive immune resistance as defined by the Tumor Inflammation Signature (TIS): results from The Cancer Genome Atlas (TCGA)

Autor: Rongze Lu, Sarah Warren, Josue Samayoa, Patrick Danaher, Amy Sullivan, Brett Wallden, Irena Pekker, Francesco M. Marincola, Alessandra Cesano
Rok vydání: 2018
Předmět:
0301 basic medicine
Cancer Research
Cell Survival
medicine.medical_treatment
Immunology
Inflammation
Pembrolizumab
Adaptive Immunity
lcsh:RC254-282
03 medical and health sciences
0302 clinical medicine
Neoplasms
Checkpoint inhibition
Gene expression
Gene signature
Biomarkers
Tumor
Tumor Microenvironment
medicine
Humans
Immunology and Allergy
Gene
Pharmacology
Tumor inflammation signature (TIS)
Genome
Human
business.industry
The Cancer Genome Atlas (TCGA)
Gene Expression Profiling
Computational Biology
Genomics
Immunotherapy
lcsh:Neoplasms. Tumors. Oncology. Including cancer and carcinogens
Prognosis
Acquired immune system
Blockade
030104 developmental biology
Oncology
030220 oncology & carcinogenesis
Mutation
Cancer research
Molecular Medicine
Tumor Escape
medicine.symptom
Transcriptome
business
Research Article
Zdroj: Journal for Immunotherapy of Cancer
Journal for ImmunoTherapy of Cancer, Vol 6, Iss 1, Pp 1-17 (2018)
ISSN: 2051-1426
DOI: 10.1186/s40425-018-0367-1
Popis: The Tumor Inflammation Signature (TIS) is an investigational use only (IUO) 18-gene signature that measures a pre-existing but suppressed adaptive immune response within tumors. The TIS has been shown to enrich for patients who respond to the anti-PD1 agent pembrolizumab. To explore this immune phenotype within and across tumor types, we applied the TIS algorithm to over 9000 tumor gene expression profiles downloaded from The Cancer Genome Atlas (TCGA). As expected based on prior evidence, tumors with known clinical sensitivity to anti-programmed cell death protein 1 (PD-1) blockade had higher average TIS scores. Furthermore, TIS scores were more variable within than between tumor types, and within each tumor type a subset of patients with elevated scores was identifiable although with different prevalence associated with each tumor type, the latter consistent with the observed clinical responsiveness to anti PD-1 blockade. Notably, TIS scores only minimally correlated with mutation load in most tumors and ranking tumors by median TIS score showed differing association to clinical sensitivity to PD-1/PD-1 ligand 1 (PD-L1) blockade than ranking of the same tumors by mutation load. The expression patterns of the TIS algorithm genes were conserved across tumor types yet appeared to be minimally prognostic in most cancers, consistent with the TIS score serving as a pan-cancer measurement of the inflamed tumor phenotype. Characterization of the prevalence and variability of TIS will lead to increased understanding of the immune status of untreated tumors and may lead to improved indication selection for testing immunotherapy agents. Electronic supplementary material The online version of this article (10.1186/s40425-018-0367-1) contains supplementary material, which is available to authorized users.
Databáze: OpenAIRE
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