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NF-κB c-Rel Is Crucial for the Regulatory T Cell Immune Checkpoint in Cancer.

Abstract：

:Regulatory T cells (Tregs) play a pivotal role in the inhibition of anti-tumor immune responses. Understanding the mechanisms governing Treg homeostasis may therefore be important for development of effective tumor immunotherapy. We have recently demonstrated a key role for the canonical nuclear factor κB (NF-κB) subunits, p65 and c-Rel, in Treg identity and function. In this report, we show that NF-κB c-Rel ablation specifically impairs the generation and maintenance of the activated Treg (aTreg) subset, which is known to be enriched at sites of tumors. Using mouse models, we demonstrate that melanoma growth is drastically reduced in mice lacking c-Rel, but not p65, in Tregs. Moreover, chemical inhibition of c-Rel function delayed melanoma growth by impairing aTreg-mediated immunosuppression and potentiated the effects of anti-PD-1 immunotherapy. Our studies therefore establish inhibition of NF-κB c-Rel as a viable therapeutic approach for enhancing checkpoint-targeting immunotherapy protocols.

journal_name

Cell

journal_title

Cell

authors

Grinberg-Bleyer Y,Oh H,Desrichard A,Bhatt DM,Caron R,Chan TA,Schmid RM,Klein U,Hayden MS,Ghosh S

doi

10.1016/j.cell.2017.08.004

subject

Has Abstract

pub_date

2017-09-07 00:00:00

pages

1096-1108.e13

issue

6

eissn

0092-8674

issn

1097-4172

pii

S0092-8674(17)30892-9

journal_volume

170

pub_type

杂志文章

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