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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.
Background:
V-domain Ig suppressor of T cell activation (VISTA) is a novel inhibitory immune-checkpoint protein. VISTA expression on tumour cells and the associated regulatory mechanisms remain unclear. We investigated VISTA expression and function in tumour cells, and evaluated its mechanism and activity.
Methods:
VISTA in tumour cells was assessed by tissue microarray analysis, immunohistochemical staining and western blot. A series of in vitro assays were used to determine the function of tumour-expressed VISTA. In vivo efficacy was evaluated in syngeneic models.
Results:
VISTA was highly expressed in human ovarian and endometrial cancers. Upregulation of VISTA in endometrial cancer was related to the methylation status of the VISTA promoter. VISTA in tumour cells suppressed T cell proliferation and cytokine production in vitro, and decreased the tumour-infiltrating CD8+ T cells in vivo. Anti-VISTA antibody prolonged the survival of tumour-bearing mice.
Conclusions:
This is the first demonstration that VISTA is highly expressed in human ovarian and endometrial cancer cells, and that anti-VISTA antibody treatment significantly prolongs the survival of mice bearing tumours expressing high levels of VISTA. The data suggest that VISTA is a novel immunosuppressive factor within the tumour microenvironment, as well as a new target for cancer immunotherapy.
Insights
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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