Targeting both tumour-associated CXCR2⁺ neutrophils and CCR2⁺ macrophages disrupts myeloid recruitment and improves chemotherapeutic responses in pancreatic ductal adenocarcinoma.

ABSTRACT:

Objective

Chemokine pathways are co-opted by pancreatic adenocarcinoma (PDAC) to facilitate myeloid cell recruitment from the bone marrow to establish an immunosuppressive tumour microenvironment (TME). Targeting tumour-associated CXCR2⁺neutrophils (TAN) or tumour-associated CCR2⁺ macrophages (TAM) alone improves antitumour immunity in preclinical models. However, a compensatory influx of an alternative myeloid subset may result in a persistent immunosuppressive TME and promote therapeutic resistance. Here, we show CCR2 and CXCR2 combined blockade reduces total tumour-infiltrating myeloids, promoting a more robust antitumour immune response in PDAC compared with either strategy alone.

Methods

Blood, bone marrow and tumours were analysed from PDAC patien

SUBMITTER: Nywening TM 

PROVIDER: S-EPMC5969359 | biostudies-literature | 2018 Jun

REPOSITORIES: biostudies-literature