{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,22]],"date-time":"2026-10-22T06:03:57Z","timestamp":1792649037281,"version":"4.5.0"},"reference-count":41,"publisher":"Oxford University Press (OUP)","issue":"6","license":[{"start":{"date-parts":[[2026,6,18]],"date-time":"2026-06-18T00:00:00Z","timestamp":1781740800000},"content-version":"vor","delay-in-days":17,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"funder":[{"name":"Ludwig Center at the University of Chicago","award":["T32AR059039"],"award-info":[{"award-number":["T32AR059039"]}]},{"DOI":"10.13039\/100007208","name":"Vanderbilt Ingram Cancer Center","doi-asserted-by":"crossref","award":["P30 CA068485"],"award-info":[{"award-number":["P30 CA068485"]}],"id":[{"id":"10.13039\/100007208","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2026,6,7]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Checkpoint inhibitors have transformed cancer treatment, yet predicting responses remains challenging. Mitochondrial quality decreases in tumor infiltrating lymphocytes and correlates with impaired antitumor immunity in animal models. Mitochondrial membrane potential (MMP) increases with T cell activation and may also indicate cellular dysfunction. Here, we assessed the MMP of tumor-associated T cells as an indicator of cell phenotypes and immunotherapy responses in non-small cell lung carcinoma and clear cell renal cell carcinoma patients. Primary tumors were collected followed by analysis of peripheral blood mononuclear cells prior to and after 3 wk on treatment with immune checkpoint inhibitors (ICIs). Peripheral blood mononuclear T cells were analyzed for MMP using tetramethylrhodamine ethyl ester (TMRE) and sorted into high and low populations. TCR\u03b2 and single-cell RNA sequencing of primary tumors identified and characterized peripheral blood T cell clones associated with the tumor microenvironment. As anticipated, ICI therapy increased the frequency of effector T cells in patients who experienced clinical benefit. TMREhigh peripheral blood T cells with tumor-matching TCR\u03b2 sequences had elevated oxidative phosphorylation gene signatures. Gene signatures of stress and exhaustion, such as Tigit and Cmc1, were also elevated in the TMREhigh CD8 T cell populations, while gene expression patterns in TMRElow cells suggested mitochondrial fitness and cell longevity. Importantly, clinical benefit from ICIs was negatively correlated with the TMREhigh CD8 T cell gene expression signature. These findings highlight a T cell population characterized by elevated MMP that correlates with exhaustion-like transcriptional states and poor response to immunotherapy.<\/jats:p>","DOI":"10.1093\/jimmun\/vkag120","type":"journal-article","created":{"date-parts":[[2026,6,18]],"date-time":"2026-06-18T02:02:34Z","timestamp":1781748154000},"source":"Crossref","is-referenced-by-count":2,"title":["Mitochondrial potential reflects T cell fitness and function during cancer immunotherapy"],"prefix":"10.1093","volume":"215","author":[{"given":"Paul L","family":"Lindau","sequence":"first","affiliation":[{"name":"Department of Medicine, Vanderbilt University Medical Center , Nashville, TN,","place":["United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alex V","family":"Nesta","sequence":"additional","affiliation":[{"name":"Vindhya Data Science , Morrisville, NC,","place":["United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Caroline E","family":"Roe","sequence":"additional","affiliation":[{"name":"Department of Cell and Developmental Biology, Vanderbilt University , Nashville, TN,","place":["United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Madelyn D","family":"Landis","sequence":"additional","affiliation":[{"name":"Department of Pathology, Microbiology, and Immunology, Vanderbilt University Medical Center , Nashville, TN,","place":["United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zaid","family":"Hatem","sequence":"additional","affiliation":[{"name":"Department of Pathology, Microbiology, and Immunology, Vanderbilt University Medical Center , Nashville, TN,","place":["United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7077-0762","authenticated-orcid":false,"given":"Allison E","family":"Sewell","sequence":"additional","affiliation":[{"name":"Department of Pathology, Microbiology, and Immunology, Vanderbilt University Medical Center , Nashville, TN,","place":["United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Allison K","family":"Blount","sequence":"additional","affiliation":[{"name":"Department of Pathology, Microbiology, and Immunology, Vanderbilt University Medical Center , Nashville, TN,","place":["United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jackie E","family":"Bader","sequence":"additional","affiliation":[{"name":"Department of Pathology, Microbiology, and Immunology, Vanderbilt University Medical Center , Nashville, TN,","place":["United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Reddy","family":"Anupama","sequence":"additional","affiliation":[{"name":"Vindhya Data Science , Morrisville, NC,","place":["United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4984-0225","authenticated-orcid":false,"given":"W Kimryn","family":"Rathmell","sequence":"additional","affiliation":[{"name":"The James Cancer Hospital and Solove Research Institute, Ohio State University Comprehensive Cancer Center , Columbus, OH,","place":["United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9428-8866","authenticated-orcid":false,"given":"Jonathan M","family":"Irish","sequence":"additional","affiliation":[{"name":"Department of Cell and Developmental Biology, Vanderbilt University , Nashville, TN,","place":["United States"]},{"name":"Vanderbilt Center for Immunobiology, Vanderbilt University Medical Center , Nashville, TN,","place":["United States"]},{"name":"Department of Pediatrics, University of Colorado Anschutz , Aurora, CO,","place":["United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4106-3396","authenticated-orcid":false,"given":"Jeffrey C","family":"Rathmell","sequence":"additional","affiliation":[{"name":"Department of Pathology, Microbiology, and Immunology, Vanderbilt University Medical Center , Nashville, TN,","place":["United States"]},{"name":"Vanderbilt Center for Immunobiology, Vanderbilt University Medical Center , Nashville, TN,","place":["United States"]},{"name":"Ben May Department for Cancer Research, University of Chicago , Chicago, IL,","place":["United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kathryn E","family":"Beckermann","sequence":"additional","affiliation":[{"name":"Department of Medicine, Vanderbilt University Medical Center , Nashville, TN,","place":["United States"]},{"name":"Tennessee Oncology, Medical Oncology , Nashville, TN,","place":["United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2026,6,17]]},"reference":[{"key":"2026090710435465000_vkag120-B1","doi-asserted-by":"crossref","first-page":"1652","DOI":"10.1016\/j.cell.2023.03.006","article-title":"Immune checkpoint therapy-current perspectives and future directions","volume":"186","author":"Sharma","year":"2023","journal-title":"Cell"},{"key":"2026090710435465000_vkag120-B2","doi-asserted-by":"crossref","first-page":"2231","DOI":"10.1016\/j.immuni.2023.09.005","article-title":"CD8(+) T cells in the cancer-immunity cycle","volume":"56","author":"Giles","year":"2023","journal-title":"Immunity"},{"key":"2026090710435465000_vkag120-B3","doi-asserted-by":"crossref","first-page":"e012096","DOI":"10.1136\/jitc-2025-012096","article-title":"Basic rules to respond to PD-1 blockade cancer immunotherapy","volume":"13","author":"Ribas","year":"2025","journal-title":"J Immunother Cancer"},{"key":"2026090710435465000_vkag120-B4","doi-asserted-by":"crossref","first-page":"abe6474","DOI":"10.1126\/science.abe6474","article-title":"Pan-cancer single-cell landscape of tumor-infiltrating T cells","volume":"374","author":"Zheng L","year":"2021","journal-title":"Science"},{"key":"2026090710435465000_vkag120-B5","doi-asserted-by":"crossref","first-page":"1053","DOI":"10.2217\/imt-2020-0336","article-title":"PD-L1 expression as a predictive biomarker for immune checkpoint inhibitors: between a dream and a nightmare","volume":"13","author":"Zouein","year":"2021","journal-title":"Immunotherapy"},{"key":"2026090710435465000_vkag120-B6","doi-asserted-by":"crossref","first-page":"274","DOI":"10.1038\/s41392-024-01979-x","article-title":"Cold and hot tumors: from molecular mechanisms to targeted therapy","volume":"9","author":"Wu","year":"2024","journal-title":"Signal Transduct Target 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