Original ResearchFull Report: Clinical—BiliaryImbalance of Genes Encoding Natural Killer Immunoglobulin-Like Receptors and Human Leukocyte Antigen in Patients With Biliary Cancer
Graphical abstract
Section snippets
Clinical Cohorts
This study was approved by the regional ethics committee in Stockholm, Sweden, and conducted in accordance with the Declaration of Helsinki. Patients with BDC were recruited at the Department of Upper Gastrointestinal Tract Diseases, Karolinska University Hospital Huddinge, Stockholm, Sweden, a specialized tertiary center for surgical treatment of liver and biliary tract cancer. Oral and written informed consent was obtained from all patients. The Swedish healthy cohort consisted of randomly
Study Design
A total of 148 Swedish patients with BDC were recruited to the study at the Department of Upper Gastrointestinal Tract Diseases, Karolinska University Hospital, a specialized tertiary center for surgical treatment of liver and biliary tract cancer. Few patients had relevant comorbidities (Figure 1A). Because PSC patients with BDCs usually receive liver transplantation, only 7% of patients in the current cohort had underlying PSC. Roughly equal numbers of patients with GBC and CCA were included
Discussion
The importance of the KIR-HLA system in human disease is clear from a plethora of work conducted over the last decades.10, 17, 19, 20, 21 However, most studies have assessed the presence or absence of single receptors in a case-control fashion without integrating functional modules governed by clusters of genes. The KIR-KIR ligand loci are unique genetic modules that have evolved with the human species and are critical for immune cell recognition of altered self.10 Based on the current
Acknowledgments
Author contributions: All authors contributed to interpretation of data. Martin Cornillet designed the study, performed experiments, analyzed the data, and drafted the manuscript. Marie Schaffer performed KIR and HLA genotyping. Ernesto Sparrelid and Bengt Isaksson contributed to recruitment and collection of the BDC cohort. Karl-Johan Malmberg, Derek Middleton, and Faviel F. Gonzalez-Galarza contributed to collection of control populations. Lena Berglin performed immunohistochemistry
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Conflicts of interest The authors disclose no conflicts.
Funding This work was funded by the Swedish Research Council, Swedish Cancer Society, Swedish Foundation for Strategic Research, Swedish Society for Medical Research, Cancer Research Foundations of Radiumhemmet, Knut and Alice Wallenberg Foundation, Novo Nordisk Foundation, Center for Innovative Medicine at Karolinska Institutet, Stockholm County Council, Karolinska Institutet, Research Council of Norway, Norwegian Cancer Foundation, and K.G. Jebsen Foundation.