CD57+ EMRA CD8+ T cells in cancer patients over 70: associations with prior chemotherapy and response to anti-PD-1/PD-L1 therapy
Abstract Background Immune ageing complicates cancer treatment in older individuals. While immunotherapy targeting the PD-1/PD-L1 pathway can reinvigorate T cells, these cells tend to become senescent with age. This study investigates different CD8+ T cell subsets usually associated with senescence,...
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BMC
2024-12-01
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| Series: | Immunity & Ageing |
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| Online Access: | https://doi.org/10.1186/s12979-024-00487-4 |
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| author | Cécile Gonnin Michelle Leemans Florence Canoui-Poitrine Morgane Lebraud Aurélien Corneau Louise Roquebert Philippe Caillet Pierre Gay Johanna Canovas Axelle Histe Catherine Blanc Carine El-Sissy Anis Larbi Johanne Poisson Pauline Ober Pascaline Boudou-Rouquette Pierre-André Natella Hélène Vallet Besma Saadaoui Richard Layese Eric Tartour Elena Paillaud Clémence Granier |
| author_facet | Cécile Gonnin Michelle Leemans Florence Canoui-Poitrine Morgane Lebraud Aurélien Corneau Louise Roquebert Philippe Caillet Pierre Gay Johanna Canovas Axelle Histe Catherine Blanc Carine El-Sissy Anis Larbi Johanne Poisson Pauline Ober Pascaline Boudou-Rouquette Pierre-André Natella Hélène Vallet Besma Saadaoui Richard Layese Eric Tartour Elena Paillaud Clémence Granier |
| author_sort | Cécile Gonnin |
| collection | DOAJ |
| description | Abstract Background Immune ageing complicates cancer treatment in older individuals. While immunotherapy targeting the PD-1/PD-L1 pathway can reinvigorate T cells, these cells tend to become senescent with age. This study investigates different CD8+ T cell subsets usually associated with senescence, in cancer patients over 70 years old who are undergoing anti-PD-1/PD-L1 immunotherapy, and examines the relationship between these senescent cells and prior chemotherapy exposure. We analyzed data from the Elderly Cancer Patient (ELCAPA) cohort, which included 35 patients enrolled between March 2018 and March 2021. Results Flow cytometry and unsupervised analysis were employed to characterize Effector Memory CD45RA+ (EMRA) and CD8+ T cell senescence at baseline, before initiating PD-1/PD-L1 therapy. EMRA cells were found to overexpress CD57 and KLRG1 compared to overall CD8+ T cells. Chemotherapy prior to anti-PD-1/PD-L1 was associated with an increased proportion of CD57+ EMRA CD8+ T cells (p = 0.009) and its granzyme B (GRZB) subset (p = 0.007). Using a 10% cut-off to define positivity, the six-month non-response tends to be associated with the CD57+ GRZB+ EMRA positivity (p = 0.097). Other CD8+ T cell subsets (EMRA, CD57+, or KLRG1+), usually associated with senescence, showed no significant association with previous chemotherapy or response to anti-PD-1/anti-PD-L1 therapy. Conclusions These findings underscore the impact of prior chemotherapy on expanding the pool of senescent T cells, particularly CD57+ EMRA CD8+ T and CD57+ GRZB+ EMRA CD8+ T cells, whose expansion could potentially affect the effectiveness of anti-PD-1/PD-L1 immunotherapy in elderly patients. This highlights the need for tailored approaches in this population. |
| format | Article |
| id | doaj-art-0216d3bceb6e46d986de33d8e2ffbf53 |
| institution | Kabale University |
| issn | 1742-4933 |
| language | English |
| publishDate | 2024-12-01 |
| publisher | BMC |
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| series | Immunity & Ageing |
| spelling | doaj-art-0216d3bceb6e46d986de33d8e2ffbf532024-12-29T12:47:14ZengBMCImmunity & Ageing1742-49332024-12-0121111210.1186/s12979-024-00487-4CD57+ EMRA CD8+ T cells in cancer patients over 70: associations with prior chemotherapy and response to anti-PD-1/PD-L1 therapyCécile Gonnin0Michelle Leemans1Florence Canoui-Poitrine2Morgane Lebraud3Aurélien Corneau4Louise Roquebert5Philippe Caillet6Pierre Gay7Johanna Canovas8Axelle Histe9Catherine Blanc10Carine El-Sissy11Anis Larbi12Johanne Poisson13Pauline Ober14Pascaline Boudou-Rouquette15Pierre-André Natella16Hélène Vallet17Besma Saadaoui18Richard Layese19Eric Tartour20Elena Paillaud21Clémence Granier22Université Paris Cité, INSERM, PARCCUniversité Paris-Est Créteil, INSERM, IMRBUniversité Paris-Est Créteil, INSERM, IMRBDepartment of Immunology, APHP, Hôpital Européen Georges Pompidou (HEGP)Sorbonne Université, Centre de recherche de Saint Antoine, CISADepartment of Immunology, APHP, Hôpital Européen Georges Pompidou (HEGP)Department of Geriatric Medicine, Hôpital Europeen Georges Pompidou, AP-HPDepartment of Geriatric Medicine, Hôpital Europeen Georges Pompidou, AP-HPDepartment of Geriatric Medicine, Hôpital Europeen Georges Pompidou, AP-HPUniversité Paris-Est Créteil, INSERM, IMRBPlateforme de Cytométrie de la Pitié-Salpêtrière (CyPS) in ParisDepartment of Immunology, APHP, Hôpital Européen Georges Pompidou (HEGP)Medical and Scientific Affairs, Beckman Coulter Life SciencesUniversité Paris Cité, Department of Geriatrics, European Georges Pompidou Hospital, Paris Cancer Institute CARPEM, Assistance-Publique Hôpitaux de Paris (AP-HP)Department of Immunology, APHP, Hôpital Européen Georges Pompidou (HEGP)Department of medical Oncology, Ariane program, Cochin hospital, Paris Cancer Institute CARPEM, Assistance-Publique Hôpitaux de Paris (AP-HP)AP-HP, Hopital Henri-Mondor, Hopital Henri-Mondor, Public Health Department and Clinical Research Unit (URC Mondor)Sorbonne Université, Institut National de la Santé et de la Recherche Médicale (INSERM), UMRS 1135, Centre d’immunologie et de Maladies Infectieuses (CIMI)Department of Geriatric Medicine, Hôpital Europeen Georges Pompidou, AP-HPUniversité Paris-Est Créteil, INSERM, IMRBUniversité Paris Cité, INSERM, PARCCDepartment of Geriatric Medicine, Hôpital Europeen Georges Pompidou, AP-HPUniversité Paris Cité, INSERM, PARCCAbstract Background Immune ageing complicates cancer treatment in older individuals. While immunotherapy targeting the PD-1/PD-L1 pathway can reinvigorate T cells, these cells tend to become senescent with age. This study investigates different CD8+ T cell subsets usually associated with senescence, in cancer patients over 70 years old who are undergoing anti-PD-1/PD-L1 immunotherapy, and examines the relationship between these senescent cells and prior chemotherapy exposure. We analyzed data from the Elderly Cancer Patient (ELCAPA) cohort, which included 35 patients enrolled between March 2018 and March 2021. Results Flow cytometry and unsupervised analysis were employed to characterize Effector Memory CD45RA+ (EMRA) and CD8+ T cell senescence at baseline, before initiating PD-1/PD-L1 therapy. EMRA cells were found to overexpress CD57 and KLRG1 compared to overall CD8+ T cells. Chemotherapy prior to anti-PD-1/PD-L1 was associated with an increased proportion of CD57+ EMRA CD8+ T cells (p = 0.009) and its granzyme B (GRZB) subset (p = 0.007). Using a 10% cut-off to define positivity, the six-month non-response tends to be associated with the CD57+ GRZB+ EMRA positivity (p = 0.097). Other CD8+ T cell subsets (EMRA, CD57+, or KLRG1+), usually associated with senescence, showed no significant association with previous chemotherapy or response to anti-PD-1/anti-PD-L1 therapy. Conclusions These findings underscore the impact of prior chemotherapy on expanding the pool of senescent T cells, particularly CD57+ EMRA CD8+ T and CD57+ GRZB+ EMRA CD8+ T cells, whose expansion could potentially affect the effectiveness of anti-PD-1/PD-L1 immunotherapy in elderly patients. This highlights the need for tailored approaches in this population.https://doi.org/10.1186/s12979-024-00487-4AgeingSenescenceImmune-ageingCancerTumourGeriatrics |
| spellingShingle | Cécile Gonnin Michelle Leemans Florence Canoui-Poitrine Morgane Lebraud Aurélien Corneau Louise Roquebert Philippe Caillet Pierre Gay Johanna Canovas Axelle Histe Catherine Blanc Carine El-Sissy Anis Larbi Johanne Poisson Pauline Ober Pascaline Boudou-Rouquette Pierre-André Natella Hélène Vallet Besma Saadaoui Richard Layese Eric Tartour Elena Paillaud Clémence Granier CD57+ EMRA CD8+ T cells in cancer patients over 70: associations with prior chemotherapy and response to anti-PD-1/PD-L1 therapy Immunity & Ageing Ageing Senescence Immune-ageing Cancer Tumour Geriatrics |
| title | CD57+ EMRA CD8+ T cells in cancer patients over 70: associations with prior chemotherapy and response to anti-PD-1/PD-L1 therapy |
| title_full | CD57+ EMRA CD8+ T cells in cancer patients over 70: associations with prior chemotherapy and response to anti-PD-1/PD-L1 therapy |
| title_fullStr | CD57+ EMRA CD8+ T cells in cancer patients over 70: associations with prior chemotherapy and response to anti-PD-1/PD-L1 therapy |
| title_full_unstemmed | CD57+ EMRA CD8+ T cells in cancer patients over 70: associations with prior chemotherapy and response to anti-PD-1/PD-L1 therapy |
| title_short | CD57+ EMRA CD8+ T cells in cancer patients over 70: associations with prior chemotherapy and response to anti-PD-1/PD-L1 therapy |
| title_sort | cd57 emra cd8 t cells in cancer patients over 70 associations with prior chemotherapy and response to anti pd 1 pd l1 therapy |
| topic | Ageing Senescence Immune-ageing Cancer Tumour Geriatrics |
| url | https://doi.org/10.1186/s12979-024-00487-4 |
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