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 language | English (US) |
|---|---|
| Article number | e1469594 |
| Journal | OncoImmunology |
| Volume | 7 |
| Issue number | 9 |
| DOIs | |
| State | Published - Sep 2 2018 |
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All Science Journal Classification (ASJC) codes
- Immunology and Allergy
- Immunology
- Oncology
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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 F.; Ehmann, W. Christopher; Rybka, Witold B.; Mineishi, Shin; Naik, Seema; Khawaja, Muhammad R.; Sivik, Jeff; Han, Junyan; Hohl, Raymond J.; Zheng, Hong.
In: OncoImmunology, Vol. 7, No. 9, e1469594, 02.09.2018.Research output: Contribution to journal › Article
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 F.
AU - Ehmann, W. Christopher
AU - Rybka, Witold B.
AU - Mineishi, Shin
AU - Naik, Seema
AU - Khawaja, Muhammad R.
AU - Sivik, Jeff
AU - Han, Junyan
AU - Hohl, Raymond J.
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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=85049783085&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85049783085&partnerID=8YFLogxK
U2 - 10.1080/2162402X.2018.1469594
DO - 10.1080/2162402X.2018.1469594
M3 - Article
C2 - 30228937
AN - SCOPUS:85049783085
VL - 7
JO - OncoImmunology
JF - OncoImmunology
SN - 2162-4011
IS - 9
M1 - e1469594
ER -