RRC ID 54701
Author Mulati K, Hamanishi J, Matsumura N, Chamoto K, Mise N, Abiko K, Baba T, Yamaguchi K, Horikawa N, Murakami R, Taki M, Budiman K, Zeng X, Hosoe Y, Azuma M, Konishi I, Mandai M.
Title VISTA expressed in tumour cells regulates T cell function.
Journal Br J Cancer
Abstract 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.
Volume 120(1)
Pages 115-127
Published 2019-1-1
DOI 10.1038/s41416-018-0313-5
PII 10.1038/s41416-018-0313-5
PMID 30382166
PMC PMC6325144
MeSH Animals B7 Antigens / genetics* CD4-Positive T-Lymphocytes / immunology CD8-Positive T-Lymphocytes / immunology Endometrial Neoplasms / genetics* Endometrial Neoplasms / immunology Endometrial Neoplasms / pathology Female Humans Immunotherapy Lymphocyte Activation / genetics Lymphocyte Activation / immunology Mice Ovarian Neoplasms / genetics* Ovarian Neoplasms / immunology Ovarian Neoplasms / pathology T-Lymphocytes / immunology* Tumor Microenvironment / genetics Tumor Microenvironment / immunology
IF 5.416
Times Cited 19
Human and Animal Cells JHUEM-2(RCB1551) JHUEM-7(RCB1677)