Mobilization of CD8+ T Cells via CXCR4 Blockade Facilitates PD-1 Checkpoint Therapy in Human Pancreatic Cancer.

ABSTRACT: PURPOSE:Pancreatic ductal adenocarcinoma (PDA) is rarely cured, and single-agent immune checkpoint inhibition has not demonstrated clinical benefit despite the presence of large numbers of CD8+ T cells. We hypothesized that tumor-infiltrating CD8+ T cells harbor latent antitumor activity that can be reactivated using combination immunotherapy. EXPERIMENTAL DESIGN:Preserved human PDA specimens were analyzed using multiplex IHC (mIHC) and T-cell receptor (TCR) sequencing. Fresh tumor was treated in organotypic slice culture to test the effects of combination PD-1 and CXCR4 blockade. Slices were analyzed using IHC, flow cytometry, and live fluorescent microscopy to assess tumor kill, in addition to T-cell expansion and mobilization. RESULTS:mIHC demonstrated fewer CD8+ T cells in juxtatumoral

SUBMITTER: Seo YD 

PROVIDER: S-EPMC6606359 | biostudies-literature | 2019 Jul

REPOSITORIES: biostudies-literature