CD103+CD8+ TRM Cells Accumulate in Tumors of Anti-PD-1-Responder Lung Cancer Patients and Are Tumor-Reactive Lymphocytes Enriched with Tc17
Summary: Accumulation of CD103+CD8+ resident memory T (TRM) cells in human lung tumors has been associated with a favorable prognosis. However, the contribution of TRM to anti-tumor immunity and to the response to immune checkpoint blockade has not been clearly established. Using quantitative multip...
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| Format: | Article |
| Language: | English |
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Elsevier
2020-10-01
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| Series: | Cell Reports Medicine |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S2666379120301695 |
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doaj-915c3d3910d847f0928d99be365b54ff |
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| record_format |
Article |
| collection |
DOAJ |
| language |
English |
| format |
Article |
| sources |
DOAJ |
| author |
Stéphanie Corgnac Ines Malenica Laura Mezquita Edouard Auclin Elodie Voilin Jamila Kacher Heloise Halse Laetitia Grynszpan Nicolas Signolle Thibault Dayris Marine Leclerc Nathalie Droin Vincent de Montpréville Olaf Mercier Pierre Validire Jean-Yves Scoazec Christophe Massard Salem Chouaib David Planchard Julien Adam Benjamin Besse Fathia Mami-Chouaib |
| spellingShingle |
Stéphanie Corgnac Ines Malenica Laura Mezquita Edouard Auclin Elodie Voilin Jamila Kacher Heloise Halse Laetitia Grynszpan Nicolas Signolle Thibault Dayris Marine Leclerc Nathalie Droin Vincent de Montpréville Olaf Mercier Pierre Validire Jean-Yves Scoazec Christophe Massard Salem Chouaib David Planchard Julien Adam Benjamin Besse Fathia Mami-Chouaib CD103+CD8+ TRM Cells Accumulate in Tumors of Anti-PD-1-Responder Lung Cancer Patients and Are Tumor-Reactive Lymphocytes Enriched with Tc17 Cell Reports Medicine CD8 TRM cells CTL Tc17 lung cancer anti-PD-1 immunotherapy tumor-infiltrating lymphocytes |
| author_facet |
Stéphanie Corgnac Ines Malenica Laura Mezquita Edouard Auclin Elodie Voilin Jamila Kacher Heloise Halse Laetitia Grynszpan Nicolas Signolle Thibault Dayris Marine Leclerc Nathalie Droin Vincent de Montpréville Olaf Mercier Pierre Validire Jean-Yves Scoazec Christophe Massard Salem Chouaib David Planchard Julien Adam Benjamin Besse Fathia Mami-Chouaib |
| author_sort |
Stéphanie Corgnac |
| title |
CD103+CD8+ TRM Cells Accumulate in Tumors of Anti-PD-1-Responder Lung Cancer Patients and Are Tumor-Reactive Lymphocytes Enriched with Tc17 |
| title_short |
CD103+CD8+ TRM Cells Accumulate in Tumors of Anti-PD-1-Responder Lung Cancer Patients and Are Tumor-Reactive Lymphocytes Enriched with Tc17 |
| title_full |
CD103+CD8+ TRM Cells Accumulate in Tumors of Anti-PD-1-Responder Lung Cancer Patients and Are Tumor-Reactive Lymphocytes Enriched with Tc17 |
| title_fullStr |
CD103+CD8+ TRM Cells Accumulate in Tumors of Anti-PD-1-Responder Lung Cancer Patients and Are Tumor-Reactive Lymphocytes Enriched with Tc17 |
| title_full_unstemmed |
CD103+CD8+ TRM Cells Accumulate in Tumors of Anti-PD-1-Responder Lung Cancer Patients and Are Tumor-Reactive Lymphocytes Enriched with Tc17 |
| title_sort |
cd103+cd8+ trm cells accumulate in tumors of anti-pd-1-responder lung cancer patients and are tumor-reactive lymphocytes enriched with tc17 |
| publisher |
Elsevier |
| series |
Cell Reports Medicine |
| issn |
2666-3791 |
| publishDate |
2020-10-01 |
| description |
Summary: Accumulation of CD103+CD8+ resident memory T (TRM) cells in human lung tumors has been associated with a favorable prognosis. However, the contribution of TRM to anti-tumor immunity and to the response to immune checkpoint blockade has not been clearly established. Using quantitative multiplex immunofluorescence on cohorts of non-small cell lung cancer patients treated with anti-PD-(L)1, we show that an increased density of CD103+CD8+ lymphocytes in immunotherapy-naive tumors is associated with greatly improved outcomes. The density of CD103+CD8+ cells increases during immunotherapy in most responder, but not in non-responder, patients. CD103+CD8+ cells co-express CD49a and CD69 and display a molecular profile characterized by the expression of PD-1 and CD39. CD103+CD8+ tumor TRM, but not CD103−CD8+ tumor-infiltrating counterparts, express Aiolos, phosphorylated STAT-3, and IL-17; demonstrate enhanced proliferation and cytotoxicity toward autologous cancer cells; and frequently display oligoclonal expansion of TCR-β clonotypes. These results explain why CD103+CD8+ TRM are associated with better outcomes in anti-PD-(L)1-treated patients. |
| topic |
CD8 TRM cells CTL Tc17 lung cancer anti-PD-1 immunotherapy tumor-infiltrating lymphocytes |
| url |
http://www.sciencedirect.com/science/article/pii/S2666379120301695 |
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doaj-915c3d3910d847f0928d99be365b54ff2020-11-25T04:07:38ZengElsevierCell Reports Medicine2666-37912020-10-0117100127CD103+CD8+ TRM Cells Accumulate in Tumors of Anti-PD-1-Responder Lung Cancer Patients and Are Tumor-Reactive Lymphocytes Enriched with Tc17Stéphanie Corgnac0Ines Malenica1Laura Mezquita2Edouard Auclin3Elodie Voilin4Jamila Kacher5Heloise Halse6Laetitia Grynszpan7Nicolas Signolle8Thibault Dayris9Marine Leclerc10Nathalie Droin11Vincent de Montpréville12Olaf Mercier13Pierre Validire14Jean-Yves Scoazec15Christophe Massard16Salem Chouaib17David Planchard18Julien Adam19Benjamin Besse20Fathia Mami-Chouaib21INSERM UMR 1186, Integrative Tumor Immunology and Immunotherapy, Gustave Roussy, Faculté de Médecine, Université Paris-Sud, Université Paris-Saclay, 94805 Villejuif, FranceINSERM UMR 1186, Integrative Tumor Immunology and Immunotherapy, Gustave Roussy, Faculté de Médecine, Université Paris-Sud, Université Paris-Saclay, 94805 Villejuif, FranceDepartment of Cancer Medicine, Gustave Roussy, Institut d’Oncologie Thoracique, Gustave Roussy, Université Paris-Saclay, 94805 Villejuif, FranceGastrointestinal and Medical Oncology Department, Hôpital Européen Georges Pompidou, Paris, FranceINSERM UMR 1186, Integrative Tumor Immunology and Immunotherapy, Gustave Roussy, Faculté de Médecine, Université Paris-Sud, Université Paris-Saclay, 94805 Villejuif, FranceINSERM UMR 1186, Integrative Tumor Immunology and Immunotherapy, Gustave Roussy, Faculté de Médecine, Université Paris-Sud, Université Paris-Saclay, 94805 Villejuif, FranceINSERM UMR 1186, Integrative Tumor Immunology and Immunotherapy, Gustave Roussy, Faculté de Médecine, Université Paris-Sud, Université Paris-Saclay, 94805 Villejuif, FranceINSERM UMR 1186, Integrative Tumor Immunology and Immunotherapy, Gustave Roussy, Faculté de Médecine, Université Paris-Sud, Université Paris-Saclay, 94805 Villejuif, FranceINSERM Unit U981, Department of Experimental Pathology, Gustave Roussy, Université Paris-Sud, Université Paris-Saclay, 94805 Villejuif, FranceDepartment of Biology and Medical Pathology, Gustave Roussy, 94805 Villejuif, FranceINSERM UMR 1186, Integrative Tumor Immunology and Immunotherapy, Gustave Roussy, Faculté de Médecine, Université Paris-Sud, Université Paris-Saclay, 94805 Villejuif, FranceDepartment of Biology and Medical Pathology, Gustave Roussy, 94805 Villejuif, FranceINSERM UMR 1186, Integrative Tumor Immunology and Immunotherapy, Gustave Roussy, Faculté de Médecine, Université Paris-Sud, Université Paris-Saclay, 94805 Villejuif, France; Hôpital Marie-Lannelongue, Service d’Anatomie Pathologique, 92350 Le-Plessis-Robinson, FranceHôpital Marie-Lannelongue, Service d’Anatomie Pathologique, 92350 Le-Plessis-Robinson, FranceInstitut Mutualiste Montsouris, Service d’Anatomie Pathologique, 75014 Paris, FranceDepartment of Biology and Medical Pathology, Gustave Roussy, 94805 Villejuif, FranceDrug Development Department, Gustave Roussy, Université Paris-Saclay, 94805 Villejuif, FranceINSERM UMR 1186, Integrative Tumor Immunology and Immunotherapy, Gustave Roussy, Faculté de Médecine, Université Paris-Sud, Université Paris-Saclay, 94805 Villejuif, FranceDepartment of Cancer Medicine, Gustave Roussy, Institut d’Oncologie Thoracique, Gustave Roussy, Université Paris-Saclay, 94805 Villejuif, FranceINSERM UMR 1186, Integrative Tumor Immunology and Immunotherapy, Gustave Roussy, Faculté de Médecine, Université Paris-Sud, Université Paris-Saclay, 94805 Villejuif, FranceDepartment of Cancer Medicine, Gustave Roussy, Institut d’Oncologie Thoracique, Gustave Roussy, Université Paris-Saclay, 94805 Villejuif, FranceINSERM UMR 1186, Integrative Tumor Immunology and Immunotherapy, Gustave Roussy, Faculté de Médecine, Université Paris-Sud, Université Paris-Saclay, 94805 Villejuif, France; Corresponding authorSummary: Accumulation of CD103+CD8+ resident memory T (TRM) cells in human lung tumors has been associated with a favorable prognosis. However, the contribution of TRM to anti-tumor immunity and to the response to immune checkpoint blockade has not been clearly established. Using quantitative multiplex immunofluorescence on cohorts of non-small cell lung cancer patients treated with anti-PD-(L)1, we show that an increased density of CD103+CD8+ lymphocytes in immunotherapy-naive tumors is associated with greatly improved outcomes. The density of CD103+CD8+ cells increases during immunotherapy in most responder, but not in non-responder, patients. CD103+CD8+ cells co-express CD49a and CD69 and display a molecular profile characterized by the expression of PD-1 and CD39. CD103+CD8+ tumor TRM, but not CD103−CD8+ tumor-infiltrating counterparts, express Aiolos, phosphorylated STAT-3, and IL-17; demonstrate enhanced proliferation and cytotoxicity toward autologous cancer cells; and frequently display oligoclonal expansion of TCR-β clonotypes. These results explain why CD103+CD8+ TRM are associated with better outcomes in anti-PD-(L)1-treated patients.http://www.sciencedirect.com/science/article/pii/S2666379120301695CD8 TRM cellsCTLTc17lung canceranti-PD-1 immunotherapytumor-infiltrating lymphocytes |