Disrupting Notch signaling related HES1 in myeloid cells reinvigorates antitumor T cell responses.

ABSTRACT:

Background

Tumor-associated macrophages (TAMs) are immunosuppressive cells within the tumor microenvironment (TME) that hinder anti-tumor immunity. Notch signaling is a pathway crucial for TAM differentiation and function. Here, we investigate the role of HES1, a downstream target of Notch signaling, in TAM-mediated immunosuppression and explore its potential as a target for cancer immunotherapy.

Methods

In this work, we constructed conditional Hes1 knockout mice to selectively delete Hes1 in TAMs. We further analyzed the TME composition, T cell infiltration and activation, and anti-tumor effects in these mice, both alone and in combination with PD-1 checkpoint blockade.

Results

Our study showed that expression levels of Notch target Hes1 were increase in TAMs and mic

SUBMITTER: Kim MS 

PROVIDER: S-EPMC11660887 | biostudies-literature | 2024 Dec

REPOSITORIES: biostudies-literature