Blockade of HVEM for Prostate Cancer Immunotherapy in Humanized Mice

The herpes virus entry mediator (HVEM) delivers a negative signal to T cells mainly through the B and lymphocyte attenuator (BTLA) molecule. Thus, HVEM/BTLA may represent novel immune checkpoint during an anti-tumor response. However, formal demonstration that HVEM can target for cancer immunotherapy is still lacking. Here, we first showed BTLA mRNA expression levels were associated with worse progression-free interval in patients prostate adenocarcinomas, indicating detrimental role progression. We then administration of monoclonal antibody human resulted twofold reduction growth cell line NOD.SCID.gc-null mice reconstituted cells. Using CRISPR/Cas9, therapeutic effect mAb depended on by tumor, no graft vs. host disease or activation spleen. In contrast, proliferation number tumor-infiltrating leukocytes increased following treatment, depletion CD8+ partly alleviated treatment’s efficacy. genes belonging various pathways was enriched leukocytes, whereas immuno-suppressive decreased, possibly resulting modifications leukocyte adhesion motility. Finally, developed simple vivo assay humanized directly demonstrate expressed tumor cell-mediated control. Our results show targeting promising strategy immunotherapy.