Tumor cell-derived IL-10 promotes cell-autonomous growth and immune escape in diffuse large B-cell lymphoma.
DLBCL mouse models
Lymphoma microenvironment
cancer immunotherapy
oncogenic STAT3 signaling
personalized treatment
Journal
Oncoimmunology
ISSN: 2162-402X
Titre abrégé: Oncoimmunology
Pays: United States
ID NLM: 101570526
Informations de publication
Date de publication:
2021
2021
Historique:
entrez:
3
12
2021
pubmed:
4
12
2021
medline:
4
1
2022
Statut:
epublish
Résumé
Diffuse large B-cell lymphoma (DLBCL) is an aggressive malignancy arising from germinal center or post-germinal center B-cells that retain many of the properties of normal B-cells. Here we show that a subset of DLBCL express the cytokine IL-10 and its receptor. The genetic ablation of IL-10 receptor signaling abrogates the autocrine STAT3 phosphorylation triggered by tumor cell-intrinsic IL-10 expression and impairs growth of DLBCL cell lines in subcutaneous and orthotopic xenotransplantation models. Furthermore, we demonstrate using an immunocompetent Myc-driven model of DLBCL that neutralization of IL-10 signaling reduces tumor growth, which can be attributed to reduced Treg infiltration, stronger intratumoral effector T-cell responses, and restored tumor-specific MHCII expression. The effects of IL-10R neutralization were phenocopied by the genetic ablation of IL-10 signaling in the Treg compartment and could be reversed by MHCII blockade. The BTK inhibitor ibrutinib effectively blocked tumor cell-intrinsic IL-10 expression and tumor growth in this Myc-driven model. Tumors from patients with high IL-10RA expression are infiltrated by higher numbers of Tregs than IL-10RA
Identifiants
pubmed: 34858727
doi: 10.1080/2162402X.2021.2003533
pii: 2003533
pmc: PMC8632300
doi:
Substances chimiques
IL10 protein, human
0
Interleukin-10
130068-27-8
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
2003533Informations de copyright
© 2021 The Author(s). Published with license by Taylor & Francis Group, LLC.
Déclaration de conflit d'intérêts
No potential conflict of interest was reported by the author(s).
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