A high OXPHOS CD8 T cell subset is predictive of immunotherapy resistance in melanoma patients.

Autor:	Li C; Department of Immunology, School of Medicine, University of Connecticut, Farmington, CT., Phoon YP; Department of Inflammation and Immunity, Cleveland Clinic, Cleveland, OH., Karlinsey K; Department of Immunology, School of Medicine, University of Connecticut, Farmington, CT., Tian YF; Department of Inflammation and Immunity, Cleveland Clinic, Cleveland, OH., Thapaliya S; Department of Inflammation and Immunity, Cleveland Clinic, Cleveland, OH., Thongkum A; Department of Inflammation and Immunity, Cleveland Clinic, Cleveland, OH., Qu L; Department of Immunology, School of Medicine, University of Connecticut, Farmington, CT., Matz AJ; Department of Immunology, School of Medicine, University of Connecticut, Farmington, CT., Cameron M; Department of Population and Quantitative Health Sciences, Case Western Reserve University, Cleveland, OH., Cameron C; Department of Nutrition, Case Western Reserve University, Cleveland, OH., Menoret A; Department of Immunology, School of Medicine, University of Connecticut, Farmington, CT., Funchain P; Taussig Cancer Institute, Cleveland Clinic, Cleveland, OH., Song JM; Taussig Cancer Institute, Cleveland Clinic, Cleveland, OH., Diaz-Montero CM; Department of Inflammation and Immunity, Cleveland Clinic, Cleveland, OH., Tamilselvan B; Department of Nutrition, Case Western Reserve University, Cleveland, OH., Golden JB; Department of Population and Quantitative Health Sciences, Case Western Reserve University, Cleveland, OH., Cartwright M; Department of Population and Quantitative Health Sciences, Case Western Reserve University, Cleveland, OH., Rodriguez A; Center for Vascular Biology, University of Connecticut, Farmington, CT., Bonin C; School of Medicine, University of Connecticut, Farmington, CT., Vella A; Department of Immunology, School of Medicine, University of Connecticut, Farmington, CT.; Institute for Systems Genomics, University of Connecticut, Farmington, CT., Zhou B; Department of Immunology, School of Medicine, University of Connecticut, Farmington, CT.; Institute for Systems Genomics, University of Connecticut, Farmington, CT., Gastman BR; Department of Inflammation and Immunity, Cleveland Clinic, Cleveland, OH.; Department of Plastic Surgery, Cleveland Clinic, Cleveland, OH.
Jazyk:	angličtina
Zdroj:	The Journal of experimental medicine [J Exp Med] 2022 Jan 03; Vol. 219 (1). Date of Electronic Publication: 2021 Nov 22.
DOI:	10.1084/jem.20202084
Abstrakt:	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. Competing Interests: Disclosures: P. Funchain reported grants from Pfizer and Bristol Myers Squibb and personal fees from Eisai outside the submitted work. A. Rodriguez reported non-financial support from Lipid Genomics during the conduct of the study and non-financial support from Lipid Genomics outside the submitted work; in addition, A. Rodriguez had a patent to LAG3 issued (Lipid Genomics). No other disclosures were reported. (© 2021 Li et al.)
Databáze:	MEDLINE
Externí odkaz:	Zobrazit plný text záznamu