1. HHLA2 is a novel immune checkpoint protein in pancreatic ductal adenocarcinoma and predicts post-surgical survival.
- Author
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Yan H, Qiu W, Koehne de Gonzalez AK, Wei JS, Tu M, Xi CH, Yang YR, Peng YP, Tsai WY, Remotti HE, Miao Y, and Su GH
- Subjects
- Carcinoma in Situ mortality, Carcinoma in Situ pathology, Carcinoma in Situ surgery, Carcinoma, Pancreatic Ductal mortality, Carcinoma, Pancreatic Ductal pathology, Carcinoma, Pancreatic Ductal surgery, Female, Humans, Immunohistochemistry, Male, Middle Aged, Pancreatectomy, Pancreatic Intraductal Neoplasms mortality, Pancreatic Intraductal Neoplasms pathology, Pancreatic Intraductal Neoplasms surgery, Pancreatic Neoplasms mortality, Pancreatic Neoplasms pathology, Pancreatic Neoplasms surgery, Retrospective Studies, Time Factors, Tissue Array Analysis, Treatment Outcome, Up-Regulation, Biomarkers, Tumor analysis, Carcinoma in Situ immunology, Carcinoma, Pancreatic Ductal immunology, Immunoglobulins analysis, Pancreatic Intraductal Neoplasms immunology, Pancreatic Neoplasms immunology
- Abstract
HHLA2 is a newly identified member of the B7 immune checkpoint family, but its function and crosstalk with immune cells is not fully understood. To gain insights into the HHLA2 expression profile and to determine the clinical significance and function of HHLA2 in pancreatic cancer, we performed immunohistochemistry (IHC) analyses on tissue microarrays (TMAs) of pancreatic ductal adenocarcinoma (PDAC, n = 92) with matched peritumoral tissues as well as in cohorts of precancerous lesions: pancreatic intraepithelial neoplasia (PanIN) and intraductal papillary mucinous neoplasm (IPMN). We found that HHLA2 was rarely detected in normal acinar, islet, and ductal cells but widely expressed from early pancreatic precancerous lesions to invasive PDAC. The overall HHLA2 positivity was 95% (19/20) in low grade PanIN and 70.73% (29/41) in IPMN. HHLA2 expression was detected in 77.17% (71/92) of the PDAC cases and was significantly associated with better prognosis in this cohort. Our findings suggest that HHLA2 may behave as a costimulatory ligand in pancreatic cancer, which differs from other B7 family members that are largely characterized as checkpoint inhibitors. Further investigation of the HHLA2 signaling pathway and its receptors is warranted by our data and may lead to novel therapeutic interventions., (Copyright © 2018 Elsevier B.V. All rights reserved.)
- Published
- 2019
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