VISTA is highly expressed on MDSCs and mediates an inhibition of T cell response in patients with AML

Liru Wang, Bei Jia, David Claxton, W. Christopher Ehmann, Witold Rybka, Shin Mineishi, Seema Naik, Muhammad R. Khawaja, Jeff Sivik, Junyan Han, Raymond Hohl, Hong Zheng

Research output: Contribution to journalArticle

2 Citations (Scopus)

Abstract

Treatment of acute myeloid leukemia (AML) remains challenging. Enhancement of anti-tumor responses by blocking negative immune regulators is a promising strategy for novel effective leukemia therapeutics. V-domain Ig suppressor of T-cell activation (VISTA) is a recently defined negative regulator mediating immune evasion in cancer. To investigate the effect of VISTA on anti-leukemia immune response in AML, we initiated a study using clinical samples collected from AML patients. Here we report that VISTA is highly expressed on myeloid-derived suppressor cells (MDSCs) in the peripheral blood of AML patients. Both the frequency and intensity of VISTA expression on MDSCs are significantly higher in newly diagnosed AML than in healthy controls. Importantly knockdown of VISTA by specific siRNA potently reduced the MDSCs-mediated inhibition of CD8 T cell activity in AML, suggesting a suppressive effect of VISTA on anti-leukemia T cell response. Furthermore, we observed a strong positive association between MDSC expression of VISTA and T cell expression of PD-1 in AML. These results support the strategy of VISTA-targeted treatment for AML and underscore the strong potential for combined blockade of VISTA and PD-1 pathways in effective leukemia control.

Original languageEnglish (US)
Article numbere1469594
JournalOncoImmunology
Volume7
Issue number9
DOIs
StatePublished - Sep 2 2018

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Acute Myeloid Leukemia
T-Lymphocytes
Leukemia
Myeloid-Derived Suppressor Cells
Immunoglobulin Domains
Immune Evasion
Small Interfering RNA
Neoplasms
Therapeutics

All Science Journal Classification (ASJC) codes

  • Immunology and Allergy
  • Immunology
  • Oncology

Cite this

@article{c3d501f7543446b7ba45b477390c7dae,
title = "VISTA is highly expressed on MDSCs and mediates an inhibition of T cell response in patients with AML",
abstract = "Treatment of acute myeloid leukemia (AML) remains challenging. Enhancement of anti-tumor responses by blocking negative immune regulators is a promising strategy for novel effective leukemia therapeutics. V-domain Ig suppressor of T-cell activation (VISTA) is a recently defined negative regulator mediating immune evasion in cancer. To investigate the effect of VISTA on anti-leukemia immune response in AML, we initiated a study using clinical samples collected from AML patients. Here we report that VISTA is highly expressed on myeloid-derived suppressor cells (MDSCs) in the peripheral blood of AML patients. Both the frequency and intensity of VISTA expression on MDSCs are significantly higher in newly diagnosed AML than in healthy controls. Importantly knockdown of VISTA by specific siRNA potently reduced the MDSCs-mediated inhibition of CD8 T cell activity in AML, suggesting a suppressive effect of VISTA on anti-leukemia T cell response. Furthermore, we observed a strong positive association between MDSC expression of VISTA and T cell expression of PD-1 in AML. These results support the strategy of VISTA-targeted treatment for AML and underscore the strong potential for combined blockade of VISTA and PD-1 pathways in effective leukemia control.",
author = "Liru Wang and Bei Jia and David Claxton and Ehmann, {W. Christopher} and Witold Rybka and Shin Mineishi and Seema Naik and Khawaja, {Muhammad R.} and Jeff Sivik and Junyan Han and Raymond Hohl and Hong Zheng",
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VISTA is highly expressed on MDSCs and mediates an inhibition of T cell response in patients with AML. / Wang, Liru; Jia, Bei; Claxton, David; Ehmann, W. Christopher; Rybka, Witold; Mineishi, Shin; Naik, Seema; Khawaja, Muhammad R.; Sivik, Jeff; Han, Junyan; Hohl, Raymond; Zheng, Hong.

In: OncoImmunology, Vol. 7, No. 9, e1469594, 02.09.2018.

Research output: Contribution to journalArticle

TY - JOUR

T1 - VISTA is highly expressed on MDSCs and mediates an inhibition of T cell response in patients with AML

AU - Wang, Liru

AU - Jia, Bei

AU - Claxton, David

AU - Ehmann, W. Christopher

AU - Rybka, Witold

AU - Mineishi, Shin

AU - Naik, Seema

AU - Khawaja, Muhammad R.

AU - Sivik, Jeff

AU - Han, Junyan

AU - Hohl, Raymond

AU - Zheng, Hong

PY - 2018/9/2

Y1 - 2018/9/2

N2 - Treatment of acute myeloid leukemia (AML) remains challenging. Enhancement of anti-tumor responses by blocking negative immune regulators is a promising strategy for novel effective leukemia therapeutics. V-domain Ig suppressor of T-cell activation (VISTA) is a recently defined negative regulator mediating immune evasion in cancer. To investigate the effect of VISTA on anti-leukemia immune response in AML, we initiated a study using clinical samples collected from AML patients. Here we report that VISTA is highly expressed on myeloid-derived suppressor cells (MDSCs) in the peripheral blood of AML patients. Both the frequency and intensity of VISTA expression on MDSCs are significantly higher in newly diagnosed AML than in healthy controls. Importantly knockdown of VISTA by specific siRNA potently reduced the MDSCs-mediated inhibition of CD8 T cell activity in AML, suggesting a suppressive effect of VISTA on anti-leukemia T cell response. Furthermore, we observed a strong positive association between MDSC expression of VISTA and T cell expression of PD-1 in AML. These results support the strategy of VISTA-targeted treatment for AML and underscore the strong potential for combined blockade of VISTA and PD-1 pathways in effective leukemia control.

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