CAR-T cell-mediated depletion of immunosuppressive tumor-associated macrophages promotes endogenous antitumor immunity and augments adoptive immunotherapy.


Journal

Nature communications
ISSN: 2041-1723
Titre abrégé: Nat Commun
Pays: England
ID NLM: 101528555

Informations de publication

Date de publication:
09 02 2021
Historique:
received: 27 04 2020
accepted: 22 12 2020
entrez: 10 2 2021
pubmed: 11 2 2021
medline: 24 2 2021
Statut: epublish

Résumé

The immunosuppressive tumor microenvironment (TME) represents a major barrier for effective immunotherapy. Tumor-associated macrophages (TAMs) are highly heterogeneous and plastic cell components of the TME which can either promote tumor progression (M2-like) or boost antitumor immunity (M1-like). Here, we demonstrate that a subset of TAMs that express folate receptor β (FRβ) possess an immunosuppressive M2-like profile. In syngeneic tumor mouse models, chimeric antigen receptor (CAR)-T cell-mediated selective elimination of FRβ

Identifiants

pubmed: 33563975
doi: 10.1038/s41467-021-20893-2
pii: 10.1038/s41467-021-20893-2
pmc: PMC7873057
doi:

Substances chimiques

Folate Receptor 2 0
Msln protein, mouse 0
Receptors, Chimeric Antigen 0
Mesothelin J27WDC343N

Types de publication

Journal Article Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't

Langues

eng

Sous-ensembles de citation

IM

Pagination

877

Subventions

Organisme : NCI NIH HHS
ID : R01 CA226983
Pays : United States

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Auteurs

Alba Rodriguez-Garcia (A)

Department of Pathology and Laboratory Medicine, Ovarian Cancer Research Center, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.
Center for Cellular Immunotherapies, Abramson Cancer Center, University of Pennsylvania, Philadelphia, PA, USA.

Rachel C Lynn (RC)

Department of Pathology and Laboratory Medicine, Ovarian Cancer Research Center, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.
Center for Cellular Immunotherapies, Abramson Cancer Center, University of Pennsylvania, Philadelphia, PA, USA.

Mathilde Poussin (M)

Department of Pathology and Laboratory Medicine, Ovarian Cancer Research Center, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.
Center for Cellular Immunotherapies, Abramson Cancer Center, University of Pennsylvania, Philadelphia, PA, USA.

Monika A Eiva (MA)

Department of Pathology and Laboratory Medicine, Ovarian Cancer Research Center, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.
Center for Cellular Immunotherapies, Abramson Cancer Center, University of Pennsylvania, Philadelphia, PA, USA.

Lauren C Shaw (LC)

Department of Pathology and Laboratory Medicine, Ovarian Cancer Research Center, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.
Center for Cellular Immunotherapies, Abramson Cancer Center, University of Pennsylvania, Philadelphia, PA, USA.

Roddy S O'Connor (RS)

Center for Cellular Immunotherapies, Abramson Cancer Center, University of Pennsylvania, Philadelphia, PA, USA.

Nicholas G Minutolo (NG)

Department of Pathology and Laboratory Medicine, Ovarian Cancer Research Center, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.
Center for Cellular Immunotherapies, Abramson Cancer Center, University of Pennsylvania, Philadelphia, PA, USA.

Victoria Casado-Medrano (V)

Department of Systems Pharmacology and Translational Therapeutics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.

Gonzalo Lopez (G)

Department of Genetics and Genomic Sciences, Icahn School of Medicine at Mount Sinai, New York, NY, USA.

Takami Matsuyama (T)

The Center for Advanced Biomedical Sciences and Swine Research, Kagoshima University, Kagoshima, Japan.

Daniel J Powell (DJ)

Department of Pathology and Laboratory Medicine, Ovarian Cancer Research Center, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA. poda@pennmedicine.upenn.edu.
Center for Cellular Immunotherapies, Abramson Cancer Center, University of Pennsylvania, Philadelphia, PA, USA. poda@pennmedicine.upenn.edu.

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Classifications MeSH