Selective targeting of GARP-LTGFβ axis in the tumor microenvironment augments PD-1 blockade via enhancing CD8⁺ T cell antitumor immunity.

ABSTRACT:

Background

Immune checkpoint blockade (ICB) has revolutionized cancer immunotherapy. However, most patients with cancer fail to respond clinically. One potential reason is the accumulation of immunosuppressive transforming growth factor β (TGFβ) in the tumor microenvironment (TME). TGFβ drives cancer immune evasion in part by inducing regulatory T cells (Tregs) and limiting CD8⁺ T cell function. Glycoprotein-A repetitions predominant (GARP) is a cell surface docking receptor for activating latent TGFβ1, TGFβ2 and TGFβ3, with its expression restricted predominantly to effector Tregs, cancer cells, and platelets.

Methods

We investigated the role of GARP in human patients with cancer by analyzing existing large databases. In addition, we generated and humanized an an

SUBMITTER: Li A 

PROVIDER: S-EPMC9472209 | biostudies-literature | 2022 Sep

REPOSITORIES: biostudies-literature