Gene Signature in Melanoma Associated With Clinical Activity: A Potential Clue to Unlock Cancer Immunotherapy
Abstract
Immunotherapeutic approaches for melanoma and other cancers can impart profound clinical benefit but only for a subset of patients. Interpatient heterogeneity could, in principle, be due to somatic differences in the tumor between individuals or alternatively be accounted for distinct germline polymorphisms in immunoregulatory genes of the host. Analysis of these possibilities has been initiated by investigating gene expression profiling of the tumor microenvironment in the context of clinical trials of cancer vaccines. Distinct gene expression profiles have been identified on pretreatment biopsies that are associated with a positive or negative clinical outcome. These observations suggest that such profiling might be useful as a predictive biomarker for clinical benefit from vaccines and other immunotherapy approaches, and analysis of specific gene products has begun to suggest new therapeutic interventions to overcome mechanisms of tumor resistance.
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Metastatic melanoma patients receiving vaccine and cytokine therapies show two broad tumor phenotypes: T cell-inflamed and non-T cell-inflamed.
“Tumor analysis from patients with metastatic melanoma receiving vaccine and cytokine therapies suggested a paradigm of two broad phenotypes characterized by the presence or absence a T cell-inflamed tumor.”
From Reimagining IDO Pathway Inhibition in Cancer Immunotherapy via Downstream Focus on the Tryptophan–Kynurenine–Aryl Hydrocarbon Axis (2019) · cites this paper as [5]
Tumors in patients who have sustained responses to checkpoint inhibitors mostly show a T cell-inflamed microenvironment before or early in treatment.
“Tumors from patients showing sustained treatment response predominately demonstrate a T cell-inflamed tumor microenvironment prior to, or early on, treatment.”
From Reimagining IDO Pathway Inhibition in Cancer Immunotherapy via Downstream Focus on the Tryptophan–Kynurenine–Aryl Hydrocarbon Axis (2019) · cites this paper as [5]
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- Authors
- Gajewski, T. F., Louahed, J., & Brichard, V. G.
- Affiliations
- University of Chicago (US)
- GlaxoSmithKline (Belgium) (BE)
- Corresponding author
- Gajewski, Thomas F.
- ORCID
- Gajewski, Thomas F.
- Venue
- The Cancer Journal
- Published
- 2010-07
- Volume
- 16
- Issue
- 4
- Pages
- 399-403
- ISSN
- 1528-9117 (ISSN-L)
- OpenAlex
- W2017251888
- Cited by
- 250
- References
- 29
- Citations by year
- 2026: 2 · 2025: 4 · 2024: 6 · 2023: 4 · 2022: 6 · 2021: 9 · 2020: 17 · 2019: 17 · 2018: 16 · 2017: 21 · 2016: 26 · 2015: 34 · 2014: 20 · 2013: 26 · 2012: 18
- FWCI
- 10.74
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- The Cancer Journal (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Health Sciences › Medicine › Oncology › Cancer Immunotherapy and Biomarkers
- Life Sciences › Immunology and Microbiology › Immunology › Immunotherapy and Immune Responses
- Health Sciences › Medicine › Oncology › Cutaneous Melanoma Detection and Management
- Keywords
- melanoma, gene expression signatures, tumor microenvironment, gene expression profiling, cancer vaccines, immunotherapy, predictive biomarkers, germline polymorphisms, immunoregulatory genes, tumor resistance, interpatient heterogeneity
- MeSH terms
- Animals, Humans, Immunity, Immunotherapy, Melanoma, Cancer Vaccines, Gene Expression Profiling, Vaccines, Subunit
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