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Targeting STAT3-VISTA axis to suppress tumor aggression and burden in acute myeloid leukemia.
- Source :
-
Journal of Hematology & Oncology . 2/27/2023, Vol. 16 Issue 1, p1-6. 6p. - Publication Year :
- 2023
-
Abstract
- The acute myeloid leukemia (AML) patients obtain limited benefits from current immune checkpoint blockades (ICBs), although immunotherapy have achieved encouraging success in numerous cancers. Here, we found that V-domain Ig suppressor of T cell activation (VISTA), a novel immune checkpoint, is highly expressed in primary AML cells and associated with poor prognosis of AML patients. Targeting VISTA by anti-VISTA mAb boosts T cell-mediated cytotoxicity to AML cells. Interestingly, high expression of VISTA is positively associated with hyperactive STAT3 in AML. Further evidence showed that STAT3 functions as a transcriptional regulator to modulate VISTA expression by directly binding to DNA response element of VISTA gene. We further develop a potent and selective STAT3 inhibitor W1046, which significantly suppresses AML proliferation and survival. W1046 remarkably enhances the efficacy of VISTA mAb by activating T cells via inhibition of STAT3 signaling and down-regulation of VISTA. Moreover, combination of W1046 and VISTA mAb achieves a significant anti-AML effect in vitro and in vivo. Overall, our findings confirm that VISTA is a potential target for AML therapy which transcriptionally regulated by STAT3 and provide a promising therapeutic strategy for immunotherapy of AML. [ABSTRACT FROM AUTHOR]
Details
- Language :
- English
- ISSN :
- 17568722
- Volume :
- 16
- Issue :
- 1
- Database :
- Academic Search Index
- Journal :
- Journal of Hematology & Oncology
- Publication Type :
- Academic Journal
- Accession number :
- 162113212
- Full Text :
- https://doi.org/10.1186/s13045-023-01410-y