Autocrine Adenosine Regulates Tumor Polyfunctional CD73+CD4+ Effector T Cells Devoid of Immune Checkpoints
| العنوان: | Autocrine Adenosine Regulates Tumor Polyfunctional CD73+CD4+ Effector T Cells Devoid of Immune Checkpoints |
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| المؤلفون: | Pedro Romero, Marion Bossennec, Isabelle Durand, Bertrand Dubois, Christelle Machon, David Bauché, Julien Faget, Nicolas Gourdin, Christophe Caux, Jérôme Guitton, Julien C. Marie, Camilla Jandus, Nicolas Chopin, Olivier Tredan, Christine Ménétrier-Caux, Céline Rodriguez, Selena Vigano |
| المساهمون: | Centre de Recherche en Cancérologie de Lyon (UNICANCER/CRCL), Centre Léon Bérard [Lyon]-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Université de Lausanne (UNIL), Centre Hospitalier Lyon Sud [CHU - HCL] (CHLS), Hospices Civils de Lyon (HCL), Institut des Sciences Pharmaceutiques et Biologiques (ISPB), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon, German Cancer Research Center - Deutsches Krebsforschungszentrum [Heidelberg] (DKFZ), Institut de Recherche en Cancérologie de Montpellier (IRCM - U1194 Inserm - UM), CRLCC Val d'Aurelle - Paul Lamarque-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM), Department of Medical Oncology [Lyon], Centre Léon Bérard [Lyon], Centre de Recherche en Cancérologie de Lyon (CRCL), Université de Lyon-Université de Lyon-Centre Léon Bérard [Lyon]-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), CRLCC Val d'Aurelle - Paul Lamarque-Université de Montpellier (UM)-Institut National de la Santé et de la Recherche Médicale (INSERM), Université de Lausanne = University of Lausanne (UNIL), Herrada, Anthony |
| المصدر: | Cancer Research, Vol. 78, No 13 (2018) pp. 3604-3618 Cancer Research Cancer Research, American Association for Cancer Research, 2018, 78 (13), pp.3604-3618. ⟨10.1158/0008-5472.CAN-17-2405⟩ Cancer research, vol. 78, no. 13, pp. 3604-3618 Cancer Research, 2018, 78 (13), pp.3604-3618. ⟨10.1158/0008-5472.CAN-17-2405⟩ |
| بيانات النشر: | American Association for Cancer Research (AACR), 2018. |
| سنة النشر: | 2018 |
| مصطلحات موضوعية: | 0301 basic medicine, Cancer Research, T-Lymphocytes, Drug Resistance, [SDV.CAN]Life Sciences [q-bio]/Cancer, Antineoplastic Agents, chemical and pharmacologic phenomena, C-C chemokine receptor type 6, CXCR3, GPI-Linked Proteins/metabolism, Helper-Inducer/immunology/metabolism, 5'-Nucleotidase/metabolism, Adenosine/metabolism, Antineoplastic Agents, Immunological/pharmacology, Antineoplastic Agents, Immunological/therapeutic use, Apyrase/metabolism, Breast Neoplasms/drug therapy, Breast Neoplasms/immunology, Breast Neoplasms/pathology, Costimulatory and Inhibitory T-Cell Receptors/antagonists & inhibitors, Costimulatory and Inhibitory T-Cell Receptors/metabolism, Drug Resistance, Neoplasm/immunology, Female, Humans, Interleukin-17/metabolism, Lymphocytes, Tumor-Infiltrating/immunology, Lymphocytes, Tumor-Infiltrating/metabolism, Ovarian Neoplasms/drug therapy, Ovarian Neoplasms/immunology, Ovarian Neoplasms/pathology, T-Lymphocytes, Helper-Inducer/immunology, T-Lymphocytes, Helper-Inducer/metabolism, T-Lymphocytes, Regulatory/immunology, T-Lymphocytes, Regulatory/metabolism, Tumor Escape/immunology, Regulatory/immunology/metabolism, Interleukin 22, 03 medical and health sciences, Immune system, [SDV.CAN] Life Sciences [q-bio]/Cancer, Lymphocytes, Autocrine signalling, Costimulatory and Inhibitory T-Cell Receptors/antagonists & inhibitors/metabolism, [SDV.MHEP] Life Sciences [q-bio]/Human health and pathology, Breast Neoplasms/drug therapy/immunology/pathology, Chemistry, Effector, Neoplasm/immunology, Immunological/pharmacology/therapeutic use, Immune checkpoint, Tumor-Infiltrating/immunology/metabolism, 030104 developmental biology, Oncology, Tumor Escape, Cancer research, Ovarian Neoplasms/drug therapy/immunology/pathology, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology |
| الوصف: | The production of CD73-derived adenosine (Ado) by Tregs has been proposed as a resistance mechanism to anti-PD-1 therapy in murine tumor models. We reported that human Tregs express the ectonucleotidase CD39, which generates AMP from ATP, but do not express the AMPase CD73. In contrast, CD73 defined a subset of effector CD4 + T cells (Teffs) enriched in polyfunctional Th1.17 cells characterized by expression of CXCR3, CCR6, and MDR1, and production of IL17A/IFNγ/IL22/GM-CSF. CD39 + Tregs selectively targeted CD73 + Teffs through cooperative degradation of ATP into Ado inhibiting and restricting the ability of CD73 + Teffs to secrete IL17A. CD73 + Teffs infiltrating breast and ovarian tumors were functionally blunted by Tregs expressing upregulated levels of CD39 and ATPase activity. Moreover, tumor-infiltrating CD73 + Teffs failed to express inhibitory immune checkpoints, suggesting that CD73 might be selected under pressure from immune checkpoint blockade therapy and thus may represent a nonredundant target for restoring antitumor immunity.Significance: Polyfunctional CD73 + T-cell effectors lacking other immune checkpoints are selectively targeted by CD39 overexpressing Tregs that dominate the breast tumor environment. Cancer Res; 78(13); 3604-18. ©2018 AACR. |
| وصف الملف: | application/pdf |
| تدمد: | 1538-7445 0008-5472 |
| URL الوصول: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::8375fbfa2c51d166ee5ae1ba8adac560 https://doi.org/10.1158/0008-5472.can-17-2405 |
| حقوق: | OPEN |
| رقم الأكسشن: | edsair.doi.dedup.....8375fbfa2c51d166ee5ae1ba8adac560 |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 15387445 00085472 |
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