Unknown

Dataset Information

0

Tumor cell-derived IL-10 promotes cell-autonomous growth and immune escape in diffuse large B-cell lymphoma.


ABSTRACT: 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-10RAlow patients. Finally, we show in 16 cases of DLBCL derived from transplant patients on immunosuppressive therapy that IL-10RA expression is less common in this cohort, and Treg infiltration is not observed.

SUBMITTER: Stirm K 

PROVIDER: S-EPMC8632300 | biostudies-literature |

REPOSITORIES: biostudies-literature

Similar Datasets

| S-EPMC3327462 | biostudies-literature
| S-EPMC6634963 | biostudies-literature
| S-EPMC8377611 | biostudies-literature
| S-EPMC8179151 | biostudies-literature
| S-EPMC7378064 | biostudies-literature
| S-EPMC5141427 | biostudies-literature
| S-EPMC5045403 | biostudies-literature
| S-EPMC4030276 | biostudies-literature
| S-EPMC9392310 | biostudies-literature
| S-EPMC3508519 | biostudies-literature