American Association for Cancer Research
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Supplementary Figure 7 from VISTA Regulates the Development of Protective Antitumor Immunity

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posted on 2023-03-30, 22:26 authored by Isabelle Le Mercier, Wenna Chen, Janet L. Lines, Maria Day, Jiannan Li, Petra Sergent, Randolph J. Noelle, Li Wang

PDF file - 21K, The therapeutic efficacy of vaccine/VISTA mab combination treatment requires T-cell mediated adaptive immune response.

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ARTICLE ABSTRACT

V-domain Ig suppressor of T-cell activation (VISTA) is a novel negative checkpoint ligand that is homologous to PD-L1 and suppresses T-cell activation. This study demonstrates the multiple mechanisms whereby VISTA relieves negative regulation by hematopoietic cells and enhances protective antitumor immunity. VISTA is highly expressed on myeloid cells and Foxp3+CD4+ regulatory cells, but not on tumor cells within the tumor microenvironment (TME). VISTA monoclonal antibody (mAb) treatment increased the number of tumor-specific T cells in the periphery and enhanced the infiltration, proliferation, and effector function of tumor-reactive T cells within the TME. VISTA blockade altered the suppressive feature of the TME by decreasing the presence of monocytic myeloid-derived suppressor cells and increasing the presence of activated dendritic cells within the tumor microenvironment. In addition, VISTA blockade impaired the suppressive function and reduced the emergence of tumor-specific Foxp3+CD4+ regulatory T cells. Consequently, VISTA mAb administration as a monotherapy significantly suppressed the growth of both transplantable and inducible melanoma. Initial studies explored a combinatorial regimen using VISTA blockade and a peptide-based cancer vaccine with TLR agonists as adjuvants. VISTA blockade synergized with the vaccine to effectively impair the growth of established tumors. Our study therefore establishes a foundation for designing VISTA-targeted approaches either as a monotherapy or in combination with additional immune-targeted strategies for cancer immunotherapy. Cancer Res; 74(7); 1933–44. ©2014 AACR.

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