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The Presence of IGHG1 in Human Pancreatic Carcinomas Is Associated With Immune Evasion Mechanisms

Li, Xiaoyan MD; Ni, Runzhou MD, PhD; Chen, Jianhua MD; Liu, Zhaoxiu MD; Xiao, Mingbing MS; Jiang, Feng BM; Lu, Cuihua MD, PhD

doi: 10.1097/MPA.0b013e318213d51b
Original Articles
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Objectives: To investigate the expression of Igγ-1 chain C region (IGHG1) in human pancreatic carcinomas and determine the biological function of IGHG1 expression in immune evasion mechanisms.

Methods: Comparative proteomic analysis was used to detect the differential expression of IGHG1 in human pancreatic cancer tissues versus adjacent noncancerous tissues, followed by confirmatory tests including quantitative real-time reverse transcription-polymerase chain reaction, Western blot analysis, immunohistochemistry, and immunofluorescence. A murine pancreatic tumor model was established by transplantation of IGHG1-overexpressing Panc02 cells. The cytotoxic responses of natural killer (NK) cells were assessed with a lactate dehydrogenase release assay.

Results: Igγ-1 chain C region was found to be present in human pancreatic cancer tissues but nearly absent or expressed lower in adjacent noncancerous tissues. In the murine pancreatic tumor model, the tumor growth was significantly accelerated from day 12 to 20 after tumor injection, and the survival time of animals was decreased. Blockage of IGHG1 led to retarded tumor growth and improved survival. The cytotoxicity assay revealed that IGHG1 downregulated the cytotoxic activity of NK cells through inhibition of antibody-dependent cellular cytotoxicity function.

Conclusions: The presence of IGHG1 in pancreatic cancer cells might constitute an important element responsible for tumor cell proliferation and immune evasion mechanisms.

Abbreviations: IGHG1 - Igγ-1 chain C region, ADCC - antibody-dependent cellular cytotoxicity, NK cells - natural killer cells, PCR - polymerase chain reaction, LDH - lactate dehydrogenase, CH - constant region of heavy chain

From the Department of Gastroenterology, Affiliated Hospital of Nantong University, Nantong, PR China.

Received for publication March 21, 2010; accepted February 2, 2011.

Reprints: Runzhou Ni, MD, PhD, Department of Gastroenterology, Affiliated Hospital of Nantong University, Room 419, Bldg 7, 20 Xisi Rd, Nantong 226001, PR China (e-mail: nirz@163.com).

Drs Li and Ni contributed equally to this study.

This work was supported by the Nantong Social Development (grants S2007028 and S2009021), by a research grant from the Jiangsu Province Health Department (grant H200923), and by the Foundation for Talents of Jiangsu Province.

© 2011 Lippincott Williams & Wilkins, Inc.