MDSC targeting with Gemtuzumab ozogamicin restores T cell immunity and immunotherapy against cancers.

ABSTRACT:

Background

Targeting of MDSCs is a major clinical challenge in the era of immunotherapy. Antibodies which deplete MDSCs in murine models can reactivate T cell responses. In humans such approaches have not developed due to difficulties in identifying targets amenable to clinical translation.

Methods

RNA-sequencing of M-MDSCs and G-MDSCs from cancer patients was undertaken. Flow cytometry and immunohistochemistry of blood and tumours determined MDSC CD33 expression. MDSCs were treated with Gemtuzumab ozogamicin and internalisation kinetics, and cell death mechanisms determined by flow cytometry, confocal microscopy and electron microscopy. Effects on T cell proliferation and CAR-T cell anti-tumour cytotoxicity were identified in the presence of Gemtuzumab ozogamicin.

Findin

SUBMITTER: Fultang L 

PROVIDER: S-EPMC6796554 | biostudies-literature | 2019 Sep

REPOSITORIES: biostudies-literature