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A high OXPHOS CD8 T cell subset is predictive of immunotherapy resistance in melanoma patients
- Source :
- The Journal of experimental medicine. 219(1)
- Publication Year :
- 2020
-
Abstract
- Immune checkpoint inhibitor (ICI) therapy continues to revolutionize melanoma treatment, but only a subset of patients respond. Major efforts are underway to develop minimally invasive predictive assays of ICI response. Using single-cell transcriptomics, we discovered a unique CD8 T cell blood/tumor-shared subpopulation in melanoma patients with high levels of oxidative phosphorylation (OXPHOS), the ectonucleotidases CD38 and CD39, and both exhaustion and cytotoxicity markers. We called this population with high levels of OXPHOS “CD8+ TOXPHOS cells.” We validated that higher levels of OXPHOS in tumor- and peripheral blood–derived CD8+ TOXPHOS cells correlated with ICI resistance in melanoma patients. We then developed an ICI therapy response predictive model using a transcriptomic profile of CD8+ TOXPHOS cells. This model is capable of discerning responders from nonresponders using either tumor or peripheral blood CD8 T cells with high accuracy in multiple validation cohorts. In sum, CD8+ TOXPHOS cells represent a critical immune population to assess ICI response with the potential to be a new target to improve outcomes in melanoma patients.
- Subjects :
- Adult
Male
medicine.medical_treatment
Immunology
Population
CD38
CD8-Positive T-Lymphocytes
Oxidative Phosphorylation
Transcriptome
Immune system
T-Lymphocyte Subsets
Outcome Assessment, Health Care
Immunology and Allergy
Medicine
Cytotoxic T cell
Humans
RNA-Seq
education
Immune Checkpoint Inhibitors
Melanoma
Cells, Cultured
Aged
education.field_of_study
Models, Genetic
business.industry
Gene Expression Profiling
Immunotherapy
Middle Aged
medicine.disease
Drug Resistance, Neoplasm
Cancer research
Female
Single-Cell Analysis
business
CD8
Algorithms
Subjects
Details
- ISSN :
- 15409538
- Volume :
- 219
- Issue :
- 1
- Database :
- OpenAIRE
- Journal :
- The Journal of experimental medicine
- Accession number :
- edsair.doi.dedup.....4f144ed948cb822a7565490e6589409e