{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,22]],"date-time":"2026-09-22T03:34:11Z","timestamp":1790048051223,"version":"4.0.1"},"reference-count":26,"publisher":"BMJ","issue":"1","license":[{"start":{"date-parts":[[2024,4,8]],"date-time":"2024-04-08T00:00:00Z","timestamp":1712534400000},"content-version":"unspecified","delay-in-days":7,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"funder":[{"name":"NIH\/NCI","award":["P30CA138292"],"award-info":[{"award-number":["P30CA138292"]}]},{"name":"National Cancer Institute of the National Institutes of Health","award":["P50CA217691"],"award-info":[{"award-number":["P50CA217691"]}]},{"name":"National Center for Georgia Clinical & Translational Science Alliance of the National Institutes of Health","award":["UL1TR002378"],"award-info":[{"award-number":["UL1TR002378"]}]}],"content-domain":{"domain":["bmj.com"],"crossmark-restriction":true},"short-container-title":["bmjonc"],"accepted":{"date-parts":[[2024,3,7]]},"published-print":{"date-parts":[[2024,4]]},"abstract":"<jats:sec>\n                    <jats:title>Objective<\/jats:title>\n                    <jats:p>Immune checkpoint inhibitors (ICI) that block the programmed cell death 1 (PD-1) pathway have shown promise with limited benefit. We and others have shown in small patient cohorts that an early proliferative CD8 T-cell response in the blood may be predictive of clinical response. However, these studies lack detailed analyses and comparisons between monotherapy and combination therapies.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods and analysis<\/jats:title>\n                    <jats:p>We analysed longitudinal blood samples from 103 patients with cancer who received \u03b1PD-1 monotherapy or combined with anti-cytotoxic T lymphocyte-associated protein 4 (\u03b1CTLA-4) or chemotherapy. Transcriptional analysis of CD8 T cells after the first treatment cycle with effector cells generated following yellow fever virus (YFV-17D) vaccine-induced infection was also compared.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      An early proliferative (Ki-67\n                      <jats:sup>+<\/jats:sup>\n                      ) CD8 T-cell response was observed after cycle 1 in 60 patients (58.3%). Patients with early-and-sustained proliferative responses (cycle 1 and beyond) had better clinical responses and survival than patients with an early-but-limited response (p=0.02). The proliferating cells had an effector-like phenotype. The transcriptional profiles of the effector-like CD8 T cells were similar irrespective of treatment type or clinical response but distinct from that of YFV-specific effector CD8 T cells.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>Our data suggest that early proliferative CD8 T-cell response in the blood is predictive, and that an early-and-sustained proliferative response may further identify patients with prolonged survival. The ICI-induced effector-like CD8 T cells are transcriptionally distinct from highly functional YFV-specific cells, suggesting opportunities for improved T-cell effector function with combination therapies for better clinical outcome.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1136\/bmjonc-2024-000328","type":"journal-article","created":{"date-parts":[[2024,4,8]],"date-time":"2024-04-08T13:25:25Z","timestamp":1712582725000},"page":"e000328","update-policy":"https:\/\/doi.org\/10.1136\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":7,"title":["Characterisation of clinical response and transcriptional profiling of proliferating CD8 T cells in the blood of cancer patients after PD-1 monotherapy or combination therapy"],"prefix":"10.1136","volume":"3","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-8624-7108","authenticated-orcid":false,"given":"Rebecca C","family":"Obeng","sequence":"first","affiliation":[{"name":"Emory Vaccine Center, Emory University School 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S","family":"Eberhardt","sequence":"additional","affiliation":[{"name":"Emory Vaccine Center, Emory University School of Medicine, Atlanta, Georgia, USA"},{"name":"Department of Microbiology and Immunology, Emory University School of Medicine, Atlanta, Georgia, USA"},{"name":"Center for Vaccinology, Geneva University Hospitals, Geneve, Gen\u00e8ve, Switzerland"},{"name":"Department of Pediatrics, Gynecology & Obstetrics, University of Geneva, Geneve, Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Donald","family":"McGuire","sequence":"additional","affiliation":[{"name":"Emory Vaccine Center, Emory University School of Medicine, Atlanta, Georgia, USA"},{"name":"Department of Microbiology and Immunology, Emory University School of Medicine, Atlanta, Georgia, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7624-5598","authenticated-orcid":false,"given":"Haydn","family":"Kissick","sequence":"additional","affiliation":[{"name":"Department of Urology, Emory University School of Medicine, Atlanta, Georgia, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Candace","family":"Daugherty","sequence":"additional","affiliation":[{"name":"Emory Vaccine Center, Emory University School of Medicine, Atlanta, Georgia, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuzi","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Biostatistics and Bioinformatics, Emory University Rollins School of Public Health, Atlanta, Georgia, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andreas","family":"Wieland","sequence":"additional","affiliation":[{"name":"Emory Vaccine Center, Emory University School of Medicine, Atlanta, Georgia, USA"},{"name":"Departments of Otolaryngology and Microbial Infection & Immunity, The Ohio State University, Columbus, Ohio, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhengjia","family":"Chen","sequence":"additional","affiliation":[{"name":"Department of Epidemiology and Biostatics, University of Illinois Chicago, Chicago, Illinois, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jeffrey M","family":"Switchenko","sequence":"additional","affiliation":[{"name":"Department of Biostatistics, Emory University Rollins School of Public Health, Atlanta, Georgia, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rathi","family":"Pillai","sequence":"additional","affiliation":[{"name":"Deparment of Hematology and Oncology, Emory University School of Medicine, Atlanta, Georgia, USA"},{"name":"Winship Cancer Institute, Emory University School of Medicine, Atlanta, Georgia, 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