Combination blockade of KLRG1 and PD-1 promotes immune control of local and disseminated cancers
| Autor: | Garvin Dodard, Céline Fugere, Corinne Leget, Benjamin Rossi, Angela Tata, Mélody Ors, Eric Vivier, Laurent Brossay |
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| Přispěvatelé: | Brown University, Innate Pharma, Centre d'Immunologie de Marseille - Luminy (CIML), Aix Marseille Université (AMU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Hôpital de la Timone [CHU - APHM] (TIMONE), DUMENIL, Anita |
| Jazyk: | angličtina |
| Rok vydání: | 2021 |
| Předmět: |
KLRG1
0301 basic medicine T cell [SDV]Life Sciences [q-bio] Programmed Cell Death 1 Receptor Immunology NK cells CD8-Positive T-Lymphocytes Mice 03 medical and health sciences checkpoint 0302 clinical medicine Immunity Neoplasms PD-1 Tumor Microenvironment cancer Animals Humans Immunology and Allergy Medicine Lectins C-Type Receptors Immunologic Receptor Immune Checkpoint Inhibitors RC254-282 ComputingMilieux_MISCELLANEOUS Original Research Tumor microenvironment business.industry Melanoma Neoplasms. Tumors. Oncology. Including cancer and carcinogens Cancer RC581-607 medicine.disease 3. Good health Blockade [SDV] Life Sciences [q-bio] Killer Cells Natural 030104 developmental biology medicine.anatomical_structure Oncology 030220 oncology & carcinogenesis Cancer research Immunotherapy Immunologic diseases. Allergy business CD8 Research Article |
| Zdroj: | OncoImmunology OncoImmunology, Taylor & Francis, 2021, 10 (1), pp.1933808. ⟨10.1080/2162402X.2021.1933808⟩ OncoImmunology, 2021, 10 (1), pp.1933808. ⟨10.1080/2162402X.2021.1933808⟩ Oncoimmunology article-version (VoR) Version of Record OncoImmunology, Vol 10, Iss 1 (2021) |
| ISSN: | 2162-4011 2162-402X |
| DOI: | 10.1080/2162402X.2021.1933808⟩ |
| Popis: | Checkpoint blockade therapy is effective against many cancers; however, new targets need to be identified to treat patients who do not respond to current treatment or demonstrate immune escape. Here, we showed that blocking the inhibitory receptor Killer cell lectin-like receptor G1 (KLRG1) enhances anti-tumor immunity mediated by NK cells and CD8+ T cells. We found that loss of KLRG1 signaling alone significantly decreased melanoma and breast cancer tumor growth in the lungs of mice. In addition, we demonstrated that KLRG1 blockade can synergize with PD-1 checkpoint therapy to increase the therapeutic efficacy compared to either treatment alone. This effect was even observed with tumors that do not respond to PD-1 checkpoint therapy. Double blockade therapy led to significantly decreased tumor size, increased frequency and activation of CD8+ T cells, and increased NK cell frequency and maturation in the tumor microenvironment. These findings demonstrate that KLRG1 is a novel checkpoint inhibitor target that affects NK and T cell anti-tumor immunity, both alone and in conjunction with established immunotherapies. |
| Databáze: | OpenAIRE |
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