Loss of the intracellular enzyme QPCTL limits chemokine function and reshapes myeloid infiltration to augment tumor immunity.

Aminoacyltransferases / genetics Animals CD8-Positive T-Lymphocytes / pathology Chemokines / metabolism Immunotherapy Leukemic Infiltration Mice Mice, Knockout Monocytes Neoplasms / immunology

Journal

Nature immunology

ISSN: 1529-2916

Titre abrégé: Nat Immunol

Pays: United States

ID NLM: 100941354

Informations de publication

Date de publication:
04 2022

Historique:

received: 29 06 2021

accepted: 10 02 2022

pubmed: 23 3 2022

medline: 9 4 2022

entrez: 22 3 2022

Statut: ppublish

Résumé

Tumor-associated macrophages are composed of distinct populations arising from monocytes or tissue macrophages, with a poorly understood link to disease pathogenesis. Here, we demonstrate that mouse monocyte migration was supported by glutaminyl-peptide cyclotransferase-like (QPCTL), an intracellular enzyme that mediates N-terminal modification of several substrates, including the monocyte chemoattractants CCL2 and CCL7, protecting them from proteolytic inactivation. Knockout of Qpctl disrupted monocyte homeostasis, attenuated tumor growth and reshaped myeloid cell infiltration, with loss of monocyte-derived populations with immunosuppressive and pro-angiogenic profiles. Antibody targeting of the receptor CSF1R, which more broadly eliminates tumor-associated macrophages, reversed tumor growth inhibition in Qpctl

Identifiants

DOI: 10.1038/s41590-022-01153-x PMID: 35314846

pubmed: 35314846

doi: 10.1038/s41590-022-01153-x

pii: 10.1038/s41590-022-01153-x

doi:

Substances chimiques

Chemokines 0

Aminoacyltransferases EC 2.3.2.-

glutaminyl-peptide cyclotransferase EC 2.3.2.5

Types de publication

Journal Article Research Support, Non-U.S. Gov't

Langues

eng

Sous-ensembles de citation

Pagination

568-580

Commentaires et corrections

Type : CommentIn

Informations de copyright

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