American Association for Cancer Research
00085472can131504-sup-fig3.pdf (94.33 kB)

Supplementary Figure 3 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 - 90KB, Human and mouse VISTA-Ig show titratable suppressive activity on human CD4 T cells. Bulk CD4 T cells were purified from human PBMCs by magnetic bead selection. Cells were labeled with CFSE, and stimulated for 5 days with 1, 2.5 or 5ug/ml of anti-CD3 co-coated with 0, 2.5, 5, or 10ug/ml of human (a and c) or mouse (b and d) VISTA-Ig. Control-Ig was added to equalize the amount of fusion protein. (a and b) Overlays showing representative CFSE profiles. Cells are gated on live, singlet CD4 positive cells. (c and d) Percentage CFSE low cells are shown as mean +/- SD. *p<0.05, **p<0.01, ***p<0.001. Data is representative of 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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