A high OXPHOS CD8 T cell subset is predictive of immunotherapy resistance in melanoma patients.
J Exp Med
; 219(1)2022 01 03.
Article
en En
| MEDLINE
| ID: mdl-34807232
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.
Texto completo:
1
Bases de datos:
MEDLINE
Asunto principal:
Fosforilación Oxidativa
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Subgrupos de Linfocitos T
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Linfocitos T CD8-positivos
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Inhibidores de Puntos de Control Inmunológico
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Inmunoterapia
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Melanoma
Tipo de estudio:
Prognostic_studies
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Risk_factors_studies
Límite:
Adult
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Aged
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Female
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Humans
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Male
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Middle aged
Idioma:
En
Revista:
J Exp Med
Año:
2022
Tipo del documento:
Article