PD-1 and TIGIT coexpression identifies a circulating CD8 T cell subset predictive of response to anti-PD-1 therapy
Background Clinical benefit from programmed cell death 1 receptor (PD-1) inhibitors relies on reinvigoration of endogenous antitumor immunity. Nonetheless, robust immunological markers, based on circulating immune cell subsets associated with therapeutic efficacy are yet to be validated.Methods We i...
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BMJ Publishing Group
2020-10-01
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| Series: | Journal for ImmunoTherapy of Cancer |
| Online Access: | https://jitc.bmj.com/content/8/2/e001631.full |
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| author | Paul Nghiem Martin Cheever Stanley R Riddell Steven P Fling Nirasha Ramchurren Nathalie Labarrière Sylvain Simon Virginie Vignard Tiffany Beauvais Brigitte Dreno Valentin Voillet Zhong Wu Camille Dabrowski Nicolas Jouand Amir Khammari Cécile Braudeau Régis Josien Olivier Adotevi Caroline Laheurte François Aubin Charles Nardin Samuel Rulli Raphael Gottardo Candice D Church |
| author_facet | Paul Nghiem Martin Cheever Stanley R Riddell Steven P Fling Nirasha Ramchurren Nathalie Labarrière Sylvain Simon Virginie Vignard Tiffany Beauvais Brigitte Dreno Valentin Voillet Zhong Wu Camille Dabrowski Nicolas Jouand Amir Khammari Cécile Braudeau Régis Josien Olivier Adotevi Caroline Laheurte François Aubin Charles Nardin Samuel Rulli Raphael Gottardo Candice D Church |
| author_sort | Paul Nghiem |
| collection | DOAJ |
| description | Background Clinical benefit from programmed cell death 1 receptor (PD-1) inhibitors relies on reinvigoration of endogenous antitumor immunity. Nonetheless, robust immunological markers, based on circulating immune cell subsets associated with therapeutic efficacy are yet to be validated.Methods We isolated peripheral blood mononuclear cell from three independent cohorts of melanoma and Merkel cell carcinoma patients treated with PD-1 inhibitor, at baseline and longitudinally after therapy. Using multiparameter flow cytometry and cell sorting, we isolated four subsets of CD8+ T cells, based on PD-1 and TIGIT expression profiles. We performed phenotypic characterization, T cell receptor sequencing, targeted transcriptomic analysis and antitumor reactivity assays to thoroughly characterize each of these subsets.Results We documented that the frequency of circulating PD-1+TIGIT+ (DPOS) CD8+ T-cells after 1 month of anti-PD-1 therapy was associated with clinical response and overall survival. This DPOS T-cell population was enriched in highly activated T-cells, tumor-specific and emerging T-cell clonotypes and T lymphocytes overexpressing CXCR5, a key marker of the CD8 cytotoxic follicular T cell population. Additionally, transcriptomic profiling defined a specific gene signature for this population as well as the overexpression of specific pathways associated with the therapeutic response.Conclusions Our results provide a convincing rationale for monitoring this PD-1+TIGIT+ circulating population as an early cellular-based marker of therapeutic response to anti-PD-1 therapy. |
| format | Article |
| id | doaj-art-e9c7452d81254d408bd2276450f26642 |
| institution | Kabale University |
| issn | 2051-1426 |
| language | English |
| publishDate | 2020-10-01 |
| publisher | BMJ Publishing Group |
| record_format | Article |
| series | Journal for ImmunoTherapy of Cancer |
| spelling | doaj-art-e9c7452d81254d408bd2276450f266422024-11-10T16:10:08ZengBMJ Publishing GroupJournal for ImmunoTherapy of Cancer2051-14262020-10-018210.1136/jitc-2020-001631PD-1 and TIGIT coexpression identifies a circulating CD8 T cell subset predictive of response to anti-PD-1 therapyPaul Nghiem0Martin Cheever1Stanley R Riddell2Steven P Fling3Nirasha Ramchurren4Nathalie Labarrière5Sylvain Simon6Virginie Vignard7Tiffany Beauvais8Brigitte Dreno9Valentin Voillet10Zhong Wu11Camille Dabrowski12Nicolas Jouand13Amir Khammari14Cécile Braudeau15Régis Josien16Olivier Adotevi17Caroline Laheurte18François Aubin19Charles Nardin20Samuel Rulli21Raphael Gottardo22Candice D Church23Fred Hutchinson Cancer Center, Seattle, Washington, USAFred Hutchinson Cancer Research Center, Seattle, Washington, USA15 Clinical Research Division, Fred Hutchinson Cancer Research Center, Seattle, Washington, USAFred Hutchinson Cancer Research Center, Seattle, Washington, USAFred Hutchinson Cancer Research Center, Seattle, Washington, USA2 LabEx IGO “Immunotherapy, Graft, Oncology”, Nantes, France3 Fred Hutchinson Cancer Research Center, Seattle, Washington, USA1 Université de Nantes, Inserm, CRCINA, F-44000 Nantes, France4 CHU of Nantes, Nantes, FranceCHU de Nantes and University de Nantes, Nantes, France3 Fred Hutchinson Cancer Research Center, Seattle, Washington, USADepartment of Cardiovascular Surgery, West China Hospital, Sichuan University, Chengdu, Sichuan, China6 Dermatology Unit, CHU Nantes, Nantes, France7 Platform Cytocell, SFR Santé Francois Bonamy, Nantes, France8Department of Dermatology, Nantes university, CHU Nantes, CIC 1413, Inserm INCIT, Nantes, France8 CHU Nantes, Laboratoire d`Immunologie, Nantes, France9 CRTI, INSERM, Université de Nantes, Nantes, FranceService d`oncologie médicale, CHU Besançon, Besançon, France10 INSERM UMR 1098, Besançon, France14 Dermatology, CHU Besancon, Besancon, France12 Dermatology Unit, Besancon Hospital, Besançon, France5 Qiagen Sciences, Frederick, Maryland, USABiostatistics Bioinformatics and Epidemiology Division, Fred Hutchinson Cancer Center, Seattle, Washington, USA14 Dermatology, Division of Dermatology, Department of Medicine, UW School of Medicine, Seattle, Washington, USABackground Clinical benefit from programmed cell death 1 receptor (PD-1) inhibitors relies on reinvigoration of endogenous antitumor immunity. Nonetheless, robust immunological markers, based on circulating immune cell subsets associated with therapeutic efficacy are yet to be validated.Methods We isolated peripheral blood mononuclear cell from three independent cohorts of melanoma and Merkel cell carcinoma patients treated with PD-1 inhibitor, at baseline and longitudinally after therapy. Using multiparameter flow cytometry and cell sorting, we isolated four subsets of CD8+ T cells, based on PD-1 and TIGIT expression profiles. We performed phenotypic characterization, T cell receptor sequencing, targeted transcriptomic analysis and antitumor reactivity assays to thoroughly characterize each of these subsets.Results We documented that the frequency of circulating PD-1+TIGIT+ (DPOS) CD8+ T-cells after 1 month of anti-PD-1 therapy was associated with clinical response and overall survival. This DPOS T-cell population was enriched in highly activated T-cells, tumor-specific and emerging T-cell clonotypes and T lymphocytes overexpressing CXCR5, a key marker of the CD8 cytotoxic follicular T cell population. Additionally, transcriptomic profiling defined a specific gene signature for this population as well as the overexpression of specific pathways associated with the therapeutic response.Conclusions Our results provide a convincing rationale for monitoring this PD-1+TIGIT+ circulating population as an early cellular-based marker of therapeutic response to anti-PD-1 therapy.https://jitc.bmj.com/content/8/2/e001631.full |
| spellingShingle | Paul Nghiem Martin Cheever Stanley R Riddell Steven P Fling Nirasha Ramchurren Nathalie Labarrière Sylvain Simon Virginie Vignard Tiffany Beauvais Brigitte Dreno Valentin Voillet Zhong Wu Camille Dabrowski Nicolas Jouand Amir Khammari Cécile Braudeau Régis Josien Olivier Adotevi Caroline Laheurte François Aubin Charles Nardin Samuel Rulli Raphael Gottardo Candice D Church PD-1 and TIGIT coexpression identifies a circulating CD8 T cell subset predictive of response to anti-PD-1 therapy Journal for ImmunoTherapy of Cancer |
| title | PD-1 and TIGIT coexpression identifies a circulating CD8 T cell subset predictive of response to anti-PD-1 therapy |
| title_full | PD-1 and TIGIT coexpression identifies a circulating CD8 T cell subset predictive of response to anti-PD-1 therapy |
| title_fullStr | PD-1 and TIGIT coexpression identifies a circulating CD8 T cell subset predictive of response to anti-PD-1 therapy |
| title_full_unstemmed | PD-1 and TIGIT coexpression identifies a circulating CD8 T cell subset predictive of response to anti-PD-1 therapy |
| title_short | PD-1 and TIGIT coexpression identifies a circulating CD8 T cell subset predictive of response to anti-PD-1 therapy |
| title_sort | pd 1 and tigit coexpression identifies a circulating cd8 t cell subset predictive of response to anti pd 1 therapy |
| url | https://jitc.bmj.com/content/8/2/e001631.full |
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