VISTA is highly expressed on MDSCs and mediates an inhibition of T cell response in patients with AML
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 me...
| Main Authors: | , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Taylor & Francis Group
2018-09-01
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| Series: | OncoImmunology |
| Subjects: | |
| Online Access: | http://dx.doi.org/10.1080/2162402X.2018.1469594 |
| _version_ | 1819060833718632448 |
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| author | Liru Wang Bei Jia David F. Claxton W Christopher Ehmann Witold B. Rybka Shin Mineishi Seema Naik Muhammad R. Khawaja Jeff Sivik Junyan Han Raymond J. Hohl Hong Zheng |
| author_facet | Liru Wang Bei Jia David F. Claxton W Christopher Ehmann Witold B. Rybka Shin Mineishi Seema Naik Muhammad R. Khawaja Jeff Sivik Junyan Han Raymond J. Hohl Hong Zheng |
| author_sort | Liru Wang |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-12-21T14:33:17Z |
| format | Article |
| id | doaj.art-61d6bff65ad14a288a8141619644fce2 |
| institution | Directory Open Access Journal |
| issn | 2162-402X |
| language | English |
| last_indexed | 2024-12-21T14:33:17Z |
| publishDate | 2018-09-01 |
| publisher | Taylor & Francis Group |
| record_format | Article |
| series | OncoImmunology |
| spelling | doaj.art-61d6bff65ad14a288a8141619644fce22022-12-21T19:00:25ZengTaylor & Francis GroupOncoImmunology2162-402X2018-09-017910.1080/2162402X.2018.14695941469594VISTA is highly expressed on MDSCs and mediates an inhibition of T cell response in patients with AMLLiru Wang0Bei Jia1David F. Claxton2W Christopher Ehmann3Witold B. Rybka4Shin Mineishi5Seema Naik6Muhammad R. Khawaja7Jeff Sivik8Junyan Han9Raymond J. Hohl10Hong Zheng11Penn State University College of MedicinePenn State University College of MedicinePenn State University College of MedicinePenn State University College of MedicinePenn State University College of MedicinePenn State University College of MedicinePenn State University College of MedicinePenn State University College of MedicinePenn State Health Milton S. Hershey Medical CenterPenn State University College of MedicinePenn State University College of MedicinePenn State University College of MedicineTreatment 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.http://dx.doi.org/10.1080/2162402X.2018.1469594acute myeloid leukemia (aml)vistaprogrammed cell death protein 1 (pd-1)immunotherapy |
| spellingShingle | Liru Wang Bei Jia David F. Claxton W Christopher Ehmann Witold B. Rybka Shin Mineishi Seema Naik Muhammad R. Khawaja Jeff Sivik Junyan Han Raymond J. Hohl Hong Zheng VISTA is highly expressed on MDSCs and mediates an inhibition of T cell response in patients with AML OncoImmunology acute myeloid leukemia (aml) vista programmed cell death protein 1 (pd-1) immunotherapy |
| title | VISTA is highly expressed on MDSCs and mediates an inhibition of T cell response in patients with AML |
| title_full | VISTA is highly expressed on MDSCs and mediates an inhibition of T cell response in patients with AML |
| title_fullStr | VISTA is highly expressed on MDSCs and mediates an inhibition of T cell response in patients with AML |
| title_full_unstemmed | VISTA is highly expressed on MDSCs and mediates an inhibition of T cell response in patients with AML |
| title_short | VISTA is highly expressed on MDSCs and mediates an inhibition of T cell response in patients with AML |
| title_sort | vista is highly expressed on mdscs and mediates an inhibition of t cell response in patients with aml |
| topic | acute myeloid leukemia (aml) vista programmed cell death protein 1 (pd-1) immunotherapy |
| url | http://dx.doi.org/10.1080/2162402X.2018.1469594 |
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