Nucleolin Therapeutic Targeting Decreases Pancreatic Cancer Immunosuppression.

ABSTRACT:

Background

The pancreatic ductal adenocarcinoma (PDAC) microenvironment is highly fibrotic and hypoxic, with poor immune cell infiltration. Recently, we showed that nucleolin (NCL) inhibition normalizes tumour vessels and impairs PDAC growth.

Methods

Immunocompetent mouse models of PDAC were treated by the pseudopeptide N6L, which selectively inhibits NCL. Tumour-infiltrating immune cells and changes in the tumour microenvironment were analysed.

Results

N6L reduced the proportion of regulatory T cells (Tregs) and myeloid-derived suppressor cells (MDSCs) and increased tumour-infiltrated T lymphocytes (TILs) with an activated phenotype. Low-dose anti-VEGFR2 treatment normalized PDAC vessels but did not modulate the immune suppressive microenvironment. RNAseq an

SUBMITTER: Ponzo M 

PROVIDER: S-EPMC9454580 | biostudies-literature | 2022 Aug

REPOSITORIES: biostudies-literature