SHP2 depletion was associated with increased T-cell activation (CD25 MFI of CD8<sup>+</sup>) by coculture of allogeneic healthy donor peripheral blood monocytes (PBMC) with SHP2 siRNA pretreated PCa cell lines.
Breaking immune tolerance by targeting CD25+ regulatory T cells is essential for the anti-tumor effect of the CTLA-4 blockade in an HLA-DR transgenic mouse model of prostate cancer.
Our study shows that like CD4(+)CD25(+) Treg cells, CD8(+) Foxp3(+) Treg cells present in prostate tumor-derived TILs suppress immune responses and that their suppressive function can be regulated by TLR8 ligands, raising the possibility that the manipulation of Treg cell function by TLR8 ligands could improve the efficacy of immunotherapy for prostate cancer patients.