机构：[a]The Department of Pathology & Cell Biology, Columbia University Medical Center, New York, NY, 10032, USA[b]Herbert Irving Comprehensive Cancer Center, Columbia University Medical Center, New York, NY, 10032, USA[c]Pancreas Center, First Affiliated Hospital of Nanjing Medical University, Nanjing, 210029, Jiangsu Province, China江苏省人民医院[d]Pancreas Institute, Nanjing Medical University, Nanjing, 210029, Jiangsu Province, China[e]Beijing Key Laboratory for Pediatric Diseases of Otolaryngology, Head and Neck Surgery, MOE Key Laboratory of Major Diseases in Children, Beijing Pediatric Research Institute, Beijing Children's Hospital, Capital Medical University, National Center for Children's Health (NCCH), Beijing, 100045, China临床科室科研平台职能科室耳鼻咽喉头颈外科临床流行病与循证医学中心儿科研究所首都医科大学附属北京儿童医院[f]Department of Otolaryngology and Head & Neck Surgery, Columbia University Medical Center, New York, NY, 10032, USA[g]Pancreas Center, Columbia University Medical Center, New York, NY, 10032, USA[h]Department of Biostatistics, Mailman School of Public Health, Columbia University, New York, NY, 10032, USA
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.
基金：
Han Yan was supported by the China Scholarship Council (CSC) for research at Columbia University Medical Center . Chun-Hua Xi was funded by the International Exchange & Cooperation Program from Nanjing Medical University (NJMU) and The First Affiliated Hospital of NJMU. Ye-Ran Yang was supported by the Morgan Stanley Children’s Hospital-Beijing Children’s Hospital Program . This study was supported by NIH / NCI R01 CA217207 and NIH / NCI R01 CA178445 .
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外文
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出版当年[2018]版：
大类|1 区医学
小类|2 区肿瘤学
最新[2023]版：
大类|1 区医学
小类|2 区肿瘤学
第一作者：
第一作者机构：[a]The Department of Pathology & Cell Biology, Columbia University Medical Center, New York, NY, 10032, USA[b]Herbert Irving Comprehensive Cancer Center, Columbia University Medical Center, New York, NY, 10032, USA[c]Pancreas Center, First Affiliated Hospital of Nanjing Medical University, Nanjing, 210029, Jiangsu Province, China[d]Pancreas Institute, Nanjing Medical University, Nanjing, 210029, Jiangsu Province, China
共同第一作者：
通讯作者：
通讯机构：[a]The Department of Pathology & Cell Biology, Columbia University Medical Center, New York, NY, 10032, USA[b]Herbert Irving Comprehensive Cancer Center, Columbia University Medical Center, New York, NY, 10032, USA[c]Pancreas Center, First Affiliated Hospital of Nanjing Medical University, Nanjing, 210029, Jiangsu Province, China[d]Pancreas Institute, Nanjing Medical University, Nanjing, 210029, Jiangsu Province, China[f]Department of Otolaryngology and Head & Neck Surgery, Columbia University Medical Center, New York, NY, 10032, USA[g]Pancreas Center, Columbia University Medical Center, New York, NY, 10032, USA[*1]Herbert Irving Comprehensive Cancer Center, Columbia University Medical Center, 1130 St. Nicholas Ave. ICRC 1004, New York, NY, 10032, USA.[*2]Pancreas Center, First Affiliated Hospital of Nanjing Medical University, 300 Guangzhou Road, Nanjing, 210029, China
推荐引用方式(GB/T 7714)：
Han Yan,Wanglong Qiu,Anne K. Koehne de Gonzalez,et al.HHLA2 is a novel immune checkpoint protein in pancreatic ductal adenocarcinoma and predicts post-surgical survival[J].CANCER LETTERS.2019,442:333-340.doi:10.1016/j.canlet.2018.11.007.
APA：
Han Yan,Wanglong Qiu,Anne K. Koehne de Gonzalez,Ji-Shu Wei,Min Tu...&Gloria H. Su.(2019).HHLA2 is a novel immune checkpoint protein in pancreatic ductal adenocarcinoma and predicts post-surgical survival.CANCER LETTERS,442,
MLA：
Han Yan,et al."HHLA2 is a novel immune checkpoint protein in pancreatic ductal adenocarcinoma and predicts post-surgical survival".CANCER LETTERS 442.(2019):333-340
医学