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
Objective 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,...
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| Format: | Article |
| Language: | English |
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BMJ Publishing Group
2024-07-01
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| Series: | BMJ Oncology |
| Online Access: | https://bmjoncology.bmj.com/content/3/1/e000328.full |
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| author | Peng Li Haydn Kissick Rebecca C Obeng Tahseen H Nasti Christiane S Eberhardt Rafi Ahmed Zhengjia Chen Warren J Leonard Suresh S Ramalingam Andreas Wieland Annapaola Mariniello Jeffrey M Switchenko Kylee Martens Daniel Y Chang Donald McGuire Candace Daugherty Yuzi Zhang Rathi Pillai Alice O Kamphorst |
| author_facet | Peng Li Haydn Kissick Rebecca C Obeng Tahseen H Nasti Christiane S Eberhardt Rafi Ahmed Zhengjia Chen Warren J Leonard Suresh S Ramalingam Andreas Wieland Annapaola Mariniello Jeffrey M Switchenko Kylee Martens Daniel Y Chang Donald McGuire Candace Daugherty Yuzi Zhang Rathi Pillai Alice O Kamphorst |
| author_sort | Peng Li |
| collection | DOAJ |
| description | Objective 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.Methods and analysis We analysed longitudinal blood samples from 103 patients with cancer who received αPD-1 monotherapy or combined with anti-cytotoxic T lymphocyte-associated protein 4 (αCTLA-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.Results An early proliferative (Ki-67+) 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.Conclusions 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. |
| format | Article |
| id | doaj-art-4cc0e384a52945fa895729f71406f6ed |
| institution | Kabale University |
| issn | 2752-7948 |
| language | English |
| publishDate | 2024-07-01 |
| publisher | BMJ Publishing Group |
| record_format | Article |
| series | BMJ Oncology |
| spelling | doaj-art-4cc0e384a52945fa895729f71406f6ed2025-01-30T09:10:10ZengBMJ Publishing GroupBMJ Oncology2752-79482024-07-013110.1136/bmjonc-2024-000328Characterisation of clinical response and transcriptional profiling of proliferating CD8 T cells in the blood of cancer patients after PD-1 monotherapy or combination therapyPeng Li0Haydn Kissick1Rebecca C Obeng2Tahseen H Nasti3Christiane S Eberhardt4Rafi Ahmed5Zhengjia Chen6Warren J Leonard7Suresh S Ramalingam8Andreas Wieland9Annapaola Mariniello10Jeffrey M Switchenko11Kylee Martens12Daniel Y Chang13Donald McGuire14Candace Daugherty15Yuzi Zhang16Rathi Pillai17Alice O Kamphorst18Laboratory of Molecular Immunology and the Immunology Center, National Heart Lung and Blood Institute, Bethesda, Maryland, USADepartment of Urology, Emory University School of Medicine, Atlanta, Georgia, USADepartment of Pathology, Case Western Reserve University School of Medicine, Cleveland, Ohio, USAEmory Vaccine Center, Emory University School of Medicine, Atlanta, Georgia, USADepartment of Microbiology and Immunology, Emory University School of Medicine, Atlanta, Georgia, USAEmory Vaccine Center, Emory University School of Medicine, Atlanta, Georgia, USADepartment of Epidemiology and Biostatics, University of Illinois Chicago, Chicago, Illinois, USALaboratory of Molecular Immunology and the Immunology Center, National Heart Lung and Blood Institute, Bethesda, Maryland, USADeparment of Hematology and Oncology, Emory University School of Medicine, Atlanta, Georgia, USAEmory Vaccine Center, Emory University School of Medicine, Atlanta, Georgia, USAEmory Vaccine Center, Emory University School of Medicine, Atlanta, Georgia, USADepartment of Biostatistics, Emory University Rollins School of Public Health, Atlanta, Georgia, USADepartment of Hematology and Medical Oncology, Oregon Health & Science University, Portland, Oregon, USAEmory Vaccine Center, Emory University School of Medicine, Atlanta, Georgia, USAEmory Vaccine Center, Emory University School of Medicine, Atlanta, Georgia, USAEmory Vaccine Center, Emory University School of Medicine, Atlanta, Georgia, USADepartment of Biostatistics and Bioinformatics, Emory University Rollins School of Public Health, Atlanta, Georgia, USADeparment of Hematology and Oncology, Emory University School of Medicine, Atlanta, Georgia, USAEmory Vaccine Center, Emory University School of Medicine, Atlanta, Georgia, USAObjective 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.Methods and analysis We analysed longitudinal blood samples from 103 patients with cancer who received αPD-1 monotherapy or combined with anti-cytotoxic T lymphocyte-associated protein 4 (αCTLA-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.Results An early proliferative (Ki-67+) 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.Conclusions 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.https://bmjoncology.bmj.com/content/3/1/e000328.full |
| spellingShingle | Peng Li Haydn Kissick Rebecca C Obeng Tahseen H Nasti Christiane S Eberhardt Rafi Ahmed Zhengjia Chen Warren J Leonard Suresh S Ramalingam Andreas Wieland Annapaola Mariniello Jeffrey M Switchenko Kylee Martens Daniel Y Chang Donald McGuire Candace Daugherty Yuzi Zhang Rathi Pillai Alice O Kamphorst 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 BMJ Oncology |
| 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 |
| title_full | 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 |
| title_fullStr | 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 |
| title_full_unstemmed | 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 |
| title_short | 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 |
| title_sort | 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 |
| url | https://bmjoncology.bmj.com/content/3/1/e000328.full |
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