PD-1 blockade restores impaired function of ex vivo expanded CD8⁺ T cells and enhances apoptosis in mismatch repair deficient EpCAM⁺PD-L1⁺ cancer cells.

ABSTRACT:

Background

Adoptive T cell therapy has been proven to be a promising modality for the treatment of cancer patients in recent years. However, the increased expression of inhibitory receptors could negatively regulate the function and persistence of transferred T cells which mediates T cell anergy, exhaustion, and tumor regression. In this study, we investigated increased cytotoxic activity after the blockade of PD-1 for effective immunotherapy.

Methods

The cytotoxic function of expanded CD8⁺ CTLs and interactions with tumor cells investigated after blocking of PD-1. Ex vivo expanded CD8⁺ CTLs were co-cultured with mismatch repair (MMR) stable or deficient (high microsatellite instability [MSI-H]) EpCAM⁺ tumor cells. The levels of IFN-γ and GrB

SUBMITTER: Kumar R 

PROVIDER: S-EPMC5516878 | biostudies-literature | 2017

REPOSITORIES: biostudies-literature