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Li C, Phoon YP, Karlinsey K, et al. A high OXPHOS CD8 T cell subset is predictive of immunotherapy resistance in melanoma patients. J Exp Med. 2021;219(1)doi: 10.1084/jem.20202084.
Li, C., Phoon, Y. P., Karlinsey, K., Tian, Y. F., Thapaliya, S., Thongkum, A., Qu, L., Matz, A. J., Cameron, M., Cameron, C., Menoret, A., Funchain, P., Song, J. M., Diaz-Montero, C. M., Tamilselvan, B., Golden, J. B., Cartwright, M., Rodriguez, A., Bonin, C., Vella, A., Zhou, B., & Gastman, B. R. (2022). A high OXPHOS CD8 T cell subset is predictive of immunotherapy resistance in melanoma patients. The Journal of experimental medicine, 219(1), . https://doi.org/10.1084/jem.20202084
Li, Chuan, et al. "A high OXPHOS CD8 T cell subset is predictive of immunotherapy resistance in melanoma patients." The Journal of experimental medicine vol. 219,1 (2022). doi: https://doi.org/10.1084/jem.20202084
Li C, Phoon YP, Karlinsey K, Tian YF, Thapaliya S, Thongkum A, Qu L, Matz AJ, Cameron M, Cameron C, Menoret A, Funchain P, Song JM, Diaz-Montero CM, Tamilselvan B, Golden JB, Cartwright M, Rodriguez A, Bonin C, Vella A, Zhou B, Gastman BR. A high OXPHOS CD8 T cell subset is predictive of immunotherapy resistance in melanoma patients. J Exp Med. 2022 Jan 03;219(1). doi: 10.1084/jem.20202084. Epub 2021 Nov 22. PMID: 34807232; PMCID: PMC8611729.
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J Exp Med. 2022 Jan 03;219(1). doi: 10.1084/jem.20202084. Epub 2021 Nov 22.

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

The Journal of experimental medicine

Chuan Li, Yee Peng Phoon, Keaton Karlinsey, Ye F Tian, Samjhana Thapaliya, Angkana Thongkum, Lili Qu, Alyssa Joyce Matz, Mark Cameron, Cheryl Cameron, Antoine Menoret, Pauline Funchain, Jung-Min Song, C Marcela Diaz-Montero, Banumathi Tamilselvan, Jackelyn B Golden, Michael Cartwright, Annabelle Rodriguez, Christopher Bonin, Anthony Vella, Beiyan Zhou, Brian R Gastman

Affiliations

  1. Department of Immunology, School of Medicine, University of Connecticut, Farmington, CT.
  2. Department of Inflammation and Immunity, Cleveland Clinic, Cleveland, OH.
  3. Department of Population and Quantitative Health Sciences, Case Western Reserve University, Cleveland, OH.
  4. Department of Nutrition, Case Western Reserve University, Cleveland, OH.
  5. Taussig Cancer Institute, Cleveland Clinic, Cleveland, OH.
  6. Center for Vascular Biology, University of Connecticut, Farmington, CT.
  7. School of Medicine, University of Connecticut, Farmington, CT.
  8. Institute for Systems Genomics, University of Connecticut, Farmington, CT.
  9. Department of Plastic Surgery, Cleveland Clinic, Cleveland, OH.

PMID: 34807232 PMCID: PMC8611729 DOI: 10.1084/jem.20202084

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.

© 2021 Li et al.

Conflict of interest statement

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 d

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