Resistance to CTLA-4 checkpoint inhibition reversed through selective elimination of granulocytic myeloid cells.

ABSTRACT:

Purpose

Local immunosuppression remains a critical problem that limits clinically meaningful response to checkpoint inhibition in patients with head and neck cancer. Here, we assessed the impact of MDSC elimination on responses to CTLA-4 checkpoint inhibition.

Experimental design

Murine syngeneic carcinoma immune infiltrates were characterized by flow cytometry. Granulocytic MDSCs (gMDSCs) were depleted and T-lymphocyte antigen-specific responses were measured. Tumor-bearing mice were treated with MDSC depletion and CTLA-4 checkpoint blockade. Immune signatures within the human HNSCC datasets from The Cancer Genome Atlas (TCGA) were analyzed and differentially expressed genes from sorted human peripheral MDSCs were examined.

Results

gMDSCs accumulated with tumor progr

SUBMITTER: Clavijo PE 

PROVIDER: S-EPMC5593525 | biostudies-literature | 2017 Aug

REPOSITORIES: biostudies-literature