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Published on: June 6, 2017
VISTA expressed in tumour cells regulates T cell function.
Kumuluzi Mulati1, Junzo Hamanishi2, Noriomi Matsumura3
1Department of Gynecology and Obstetrics, Kyoto University Graduate School of Medicine, Kyoto, Japan.
V-domain Ig suppressor of T cell activation (VISTA) is highly expressed in ovarian and endometrial cancers. Targeting VISTA with antibodies may offer a new immunotherapy strategy for these cancers.
Area of Science:
- Immunology
- Oncology
- Cancer Research
Background:
- V-domain Ig suppressor of T cell activation (VISTA) is an inhibitory immune-checkpoint protein.
- VISTA expression and regulatory mechanisms in tumor cells are not well understood.
- This study investigates VISTA expression and function in tumor cells.
Purpose of the Study:
- To investigate VISTA expression and function in tumor cells.
- To evaluate the mechanism and activity of VISTA in the tumor microenvironment.
- To assess VISTA as a potential target for cancer immunotherapy.
Main Methods:
- Tissue microarray analysis, immunohistochemistry, and western blot were used to assess VISTA expression.
- In vitro assays were performed to determine the function of tumor-expressed VISTA.
- In vivo efficacy was evaluated in syngeneic tumor models.
Main Results:
- VISTA was highly expressed in human ovarian and endometrial cancers.
- Tumor-expressed VISTA suppressed T cell proliferation and cytokine production in vitro.
- VISTA expression in tumors reduced CD8+ T cell infiltration in vivo, and anti-VISTA antibody treatment prolonged survival in mice.
Conclusions:
- VISTA is highly expressed in ovarian and endometrial cancer cells, acting as an immunosuppressive factor.
- Anti-VISTA antibody treatment significantly prolongs survival in mice with VISTA-expressing tumors.
- VISTA represents a novel therapeutic target for cancer immunotherapy.
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