American Association for Cancer Research
00085472can131504-sup-fig4.pdf (24.12 kB)

Supplementary Figure 4 from VISTA Is an Immune Checkpoint Molecule for Human T Cells

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journal contribution
posted on 2023-03-30, 22:24 authored by J. Louise Lines, Eirini Pantazi, Justin Mak, Lorenzo F. Sempere, Li Wang, Samuel O'Connell, Sabrina Ceeraz, Arief A. Suriawinata, Shaofeng Yan, Marc S. Ernstoff, Randolph Noelle

PDF file - 20KB, The suppressive effect of VISTA is stable. Bulk CD4 T cells were purified from human PBMCs by magnetic bead selection. Cells were CFSE labeled and stimulated for 3 days with 2.5ug/ml anti-CD3 co-coated with 0, 2.5, 5 or 10ug/ml of VISTA-Ig. Control-Ig was used to bring the concentration of fusion protein to 10ug/ml in all wells. Cells were then moved to anti-CD3 in the absence of fusion protein. Percentage CFSE low cells are shown as mean +/- SD. Data is representative of at least two separate experiments.



V-domain Ig suppressor of T cell activation (VISTA) is a potent negative regulator of T-cell function that is expressed on hematopoietic cells. VISTA levels are heightened within the tumor microenvironment, in which its blockade can enhance antitumor immune responses in mice. In humans, blockade of the related programmed cell death 1 (PD-1) pathway has shown great potential in clinical immunotherapy trials. Here, we report the structure of human VISTA and examine its function in lymphocyte negative regulation in cancer. VISTA is expressed predominantly within the hematopoietic compartment with highest expression within the myeloid lineage. VISTA-Ig suppressed proliferation of T cells but not B cells and blunted the production of T-cell cytokines and activation markers. Our results establish VISTA as a negative checkpoint regulator that suppresses T-cell activation, induces Foxp3 expression, and is highly expressed within the tumor microenvironment. By analogy to PD-1 and PD-L1 blockade, VISTA blockade may offer an immunotherapeutic strategy for human cancer. Cancer Res; 74(7); 1924–32. ©2013 AACR.

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