Zelin Hou1, Yu Pan1, Qinglin Fei1,2, Yali Lin1, Yuanyuan Zhou3, Ying Liu4, Hongdan Guan5, Xunbin Yu6, Xianchao Lin1, Fengchun Lu1, Heguang Huang7. 1. Department of General Surgery, Fujian Medical University Union Hospital, No. 29 Xinquan Road, Fuzhou, 350001, People's Republic of China. 2. The Cancer Center, Fujian Medical University Union Hospital, Fuzhou, 350001, China. 3. Department of Geriatrics, Fujian Medical University Union Hospital, Fuzhou, 350001, China. 4. Department of Endocrinology, Quanzhou Hospital of Traditional Chinese Medicine, Quanzhou, 362000, China. 5. Department of Radiation Oncology, Fujian Medical University Union Hospital, Fuzhou, 350001, China. 6. Department of Pathology, Fujian Provincialial Hospital, Fuzhou, 350001, China. 7. Department of General Surgery, Fujian Medical University Union Hospital, No. 29 Xinquan Road, Fuzhou, 350001, People's Republic of China. heguanghuang22@163.com.
Abstract
OBJECTIVE: V-domain Ig suppressor of T cell activation (VISTA) is a novel immune checkpoint protein that belongs to the B7 family. The aim of this study was to investigate the prognostic significance and therapeutic potential of VISTA in patients with pancreatic cancer. METHODS: Using immunohistochemistry (IHC), we examined the expression of VISTA and demonstrated the associations between the VISTA and overall survival in 223 PDAC patients from 2 different unrelated retrospective cohorts. The multiplex immunofluorescence was performed to illuminate the relationship between VISTA expression and tumor-infiltrating immune cell subclusters of PDAC. We also verified the findings in The Cancer Genome Atlas (TCGA) dataset. The anti-tumor effect of anti-VISTA therapy was studied by the mouse model with liver metastases of PDAC. RESULTS: The VISTA protein was highly expressed in 25.6% of tumor cells (TCs), 38.1% of immune cells, and 26.0% of endothelial cells in 223 PDAC tumor tissues. VISTA expression in TCs was significantly associated with prolonged overall survival. Multiplex immunofluorescence analysis revealed that VISTA level was positively correlated with CD68+ macrophages, CD3+ T cells, and CD19+ B cells in PDAC. However, a higher expression level of VISTA was detected in tumor-infiltrating CD68+ macrophages than in CD3+ T and CD19+ B cells. Furthermore, anti-VISTA antibody treatment significantly reduced the number of metastatic nodules in livers of mouse models of PDAC with liver metastases. CONCLUSION: VISTA expressed in TCs is associated with a favorable prognosis in PDAC. Moreover, immunotherapy with anti-VISTA antibodies may potentially be an effective treatment strategy against PDAC.
OBJECTIVE:V-domain Ig suppressor of T cell activation (VISTA) is a novel immune checkpoint protein that belongs to the B7 family. The aim of this study was to investigate the prognostic significance and therapeutic potential of VISTA in patients with pancreatic cancer. METHODS: Using immunohistochemistry (IHC), we examined the expression of VISTA and demonstrated the associations between the VISTA and overall survival in 223 PDACpatients from 2 different unrelated retrospective cohorts. The multiplex immunofluorescence was performed to illuminate the relationship between VISTA expression and tumor-infiltrating immune cell subclusters of PDAC. We also verified the findings in The Cancer Genome Atlas (TCGA) dataset. The anti-tumor effect of anti-VISTA therapy was studied by the mouse model with liver metastases of PDAC. RESULTS: The VISTA protein was highly expressed in 25.6% of tumor cells (TCs), 38.1% of immune cells, and 26.0% of endothelial cells in 223 PDACtumor tissues. VISTA expression in TCs was significantly associated with prolonged overall survival. Multiplex immunofluorescence analysis revealed that VISTA level was positively correlated with CD68+ macrophages, CD3+ T cells, and CD19+ B cells in PDAC. However, a higher expression level of VISTA was detected in tumor-infiltrating CD68+ macrophages than in CD3+ T and CD19+ B cells. Furthermore, anti-VISTA antibody treatment significantly reduced the number of metastatic nodules in livers of mouse models of PDAC with liver metastases. CONCLUSION:VISTA expressed in TCs is associated with a favorable prognosis in PDAC. Moreover, immunotherapy with anti-VISTA antibodies may potentially be an effective treatment strategy against PDAC.
Entities:
Keywords:
Biomarker; Immune checkpoints; Immunotherapy; Pancreatic cancer; VISTA
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