Shp-1 regulates the activity of low-affinity T cells specific to endogenous self-antigen during melanoma tumor growth and drives resistance to immune checkpoint inhibition.

ABSTRACT:

Background

The presence of activated CD8 T cells in the tumor microenvironment is correlated with an effective immune response to immune checkpoint inhibitor (ICI) therapy. However, ICI predominantly targets high-affinity T cells, which may be less abundant in tumors with few neoantigens. Targeting the intracellular phosphatase Src homology region 2 domain-containing phosphatase-1 (Shp-1) in combination with ICI lowers the T cell activation threshold and enhances the ability of low-affinity T cells to mount a productive antitumor response.

Methods

In this study, we sought to determine whether temporal inhibition of Shp-1 during active tumor growth could rescue the activity of low-affinity T cells specific for endogenous self-antigens. To address this question, we implanted Y

SUBMITTER: Matous JG 

PROVIDER: S-EPMC12007028 | biostudies-literature | 2025 Apr

REPOSITORIES: biostudies-literature