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Acidity changes immunology: a new VISTA pathway

Hypoxia and acidity in the tumor microenvironment promote resistance to immunotherapy. Hypoxia upregulates multiple immunoinhibitory pathways, including VISTA, and acidity enables VISTA to interact with PSGL-1 to inhibit immune activation selectively in the acidic tumor microenvironment.

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Fig. 1: Acid activates the VISTA pathway.


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Correspondence to Gordon J. Freeman.

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Competing interests

G.J.F. has served on advisory boards for Roche, Bristol-Myers-Squibb, Xios, Origimed, Triursus, iTeos and NextPoint; has equity in NextPoint, Triursus and Xios; and has the following patents on the PD-L1/PD-L2/PD-1 pathway and tumor immunotherapy: United States patents US 6808710, US 6936704, US 7038013, US 7101550, US 7105328, US 7432059, US 7635757, US 7638492, US 7700301, US 7709214, US 7722868, US 8552154, US 8652465, US 9102727, US 9457080, US 9598491, US 9683048, US 9815898, US 9845356, US 9988452, US 10011656, US 10202454, US 10370446 and US 10370448.

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Mahoney, K.M., Freeman, G.J. Acidity changes immunology: a new VISTA pathway. Nat Immunol 21, 13–16 (2020).

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