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Review
. 2019 Apr:42:101308.
doi: 10.1016/j.smim.2019.101308.

VISTA: a novel immunotherapy target for normalizing innate and adaptive immunity

Mohamed A ElTanbouly  1 , Walburga Croteau  1 , Randolph J Noelle  2 , J Louise Lines  3
Affiliations
Review

VISTA: a novel immunotherapy target for normalizing innate and adaptive immunity

Mohamed A ElTanbouly et al. Semin Immunol. 2019 Apr.

Abstract

V-domain Ig suppressor of T cell activation (VISTA) is a novel checkpoint regulator with limited homology to other B7 family members. The constitutive expression of VISTA on both the myeloid and T lymphocyte lineages coupled to its important role in regulating innate and adaptive immune responses, qualifies VISTA to be a promising target for immunotherapeutic intervention. Studies have shown differential impact of agonistic and antagonistic targeting of VISTA, providing a unique landscape for influencing the outcome of cancer and inflammatory diseases.

Keywords: Agonist; Antagonist; Autoimmunity; Cancer immunotherapy; Immune checkpoint; VISTA.

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Figures

Fig. 1.
Fig. 1.
Confocal microscopy reveals VISTA localization within endosomal compartments. Thioglycolate-elicited peritoneal macrophages from 8-week old C57BL/6 mice were allowed to adhere on glass coverslips for 2h followed by fixing and staining. In all panels, VISTA was stained with an anti-VISTA antibody (MH5A at 1:100) or isotype control Ab, secondary staining with anti-hamster IgG-Biotin (1:250) and detected using Streptavidin DyLight 649 (1:250). VISTA KO peritoneal macrophages were used as a biological control to validate specific staining of VISTA. For all other proteins, secondary staining was performed using goat anti-rabbit IgG A488 (1:1000, green) A) VISTA staining of macrophages counterstained with DAPI (Blue), B) VISTA staining (violet) with Rab11 staining (green). A representative cell is presented singly-stained with either VISTA (red) or Rab11 (green 1:100) to compare overlapping patterns of expression C) VISTA staining (red) with EEA-1 (green, 1:100) counterstained with DAPI (blue) D) VISTA staining (red) with Rab4 (green 1:200) and E) VISTA (red) with TMEM165 (green).
Fig. 2.
Fig. 2.
VISTA is prominently expressed within myeloid and T cells in spleens and tumors. Multiplex IHC performed with the Opal Multiplex Manual IHC Kit (PerkinElmer NEL811001KT) on spleen (A) and tumor (B) from mice bearing CT26 colon tumors.
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