[Gemcitabine augments major histocompatibility complex class I-related chain A expression in pancreatic cancer].

Abstract

Major histocompatibility complex(MHC)class I related chain A( MICA) expressed on the cell surface of tumor cells functions as a ligand for natural killer group 2, member D (NKG2D), an important immunoreceptor expressed on natural killer ( NK ), CD8, and γδT cells. The interaction of MICA and NKG2D stimulates NK cell-mediated cytotoxicity. Gemcitabine (GEM), a key drug for pancreatic cancer treatment, stimulates the expression of cell surface MICA in tumor cells to enhance the cytotoxicity of NK cells. The combination of GEM and S-1 is used as a neoadjuvant chemotherapy (NAC) drug for pancreatic cancer in our department. We investigated the effect of GEM on pancreatic cancer. On immunohistochemistry, MICA expression was positive in 11 of 13 (85%) pancreatic ductal adenocarcinomas in the NAC group, and in 4 of 11 (36%) in the placebo control group. There was a greater proportion of NKG2D-positive cells in 5 random samples taken from both the NAC groups( 10 of 13, 77%) than in equivalent samples taken from the placebo control group( 3 of 11, 27%). In addition, CD16-positive cells were more prevalent among NK, CD8, and γδT cells in the NAC group( 9 of 13, 69%) than in the placebo control group( 3 of 11, 27%). Therefore, GEM may induce MICA expression on the surface of pancreatic cells and thus cause the accumulation of NKG2D and CD16-positive cells around tumors.

• Authors: Tomoharu Miyashita, Hidehiro Tajima, Masatoshi Shoji, Shinichi Nakanuma, Seisho Sakai, Isamu Makino, Hironori Hayashi, Hisatoshi Nakagawara, Hiroyuki Takamura, Hirohisa Kitagawa, Tetsuo Ohta
• Journal: Gan to kagaku ryoho. Cancer & chemotherapy (Gan To Kagaku Ryoho) Vol. 40 Issue 12 Pg. 1600-2 (Nov 2013) ISSN: 0385-0684 [Print] Japan
• PMID: 24393861 (Publication Type: English Abstract, Journal Article)

Chemical References

• Antimetabolites, Antineoplastic
• Histocompatibility Antigens Class I
• MHC class I-related chain A
• Deoxycytidine
• Gemcitabine

Topics

• Aged
• Antimetabolites, Antineoplastic (therapeutic use)
• Deoxycytidine (analogs & derivatives, therapeutic use)
• Female
• Histocompatibility Antigens Class I (immunology)
• Humans
• Killer Cells, Natural (immunology)
• Male
• Middle Aged
• Neoplasm Invasiveness
• Pancreatic Neoplasms (drug therapy, immunology, pathology)
• T-Lymphocytes (immunology)
• Gemcitabine