Distributions of non-expressed MHC class I chain related A (MICA) and NKG2D receptor polymorphism in cholangiocarcinoma

Abstract

Abstract MICA is an MHC class I like molecule functioning as a ligand of an activating receptor, NKG2D. This molecule is up regulated under stress conditions especially of cancerous cells. Thus, lacking of this molecule could lead to an impairment of immune surveillance and the progression of cancer. In addition to the ligand, polymorphism of NKG2D is also impact the activating function of immune cells. Thus, we have investigated the distributions of non-expressed (MICA*010) allele and deletion of the MICA gene in 365 northeastern Thais (NET) and 121 patients of cholangiocarcinoma (CCA) which is the most common form of intrahepatic cancer of NET with the highest prevalence in the world. MICA*010 and NKG2D typing were performed by PCR-SSP and the MICA deletion by multiplex PCR using three pairs of primers. The prevalence of MICA deletion was higher in CCA than that of NET (% allele frequency (%AF) of 0.25 vs 1.7: Pc = 0.036) with a relative risk of 6.21. Although the %AF of MICA*010 in CCA was not significantly different from NET (34.7 vs 34.3; p-value = 0.96), the prevalence of heterozygous MICA*010 with MICA null in CCA was significantly higher than that of NET (%AF = 0.29 VS 3; Pc = 0.037; RR = 3.39). The results suggested that individuals carrying the MICA null allele with or without the non-expressed allele were more susceptible to develop CCA implicating the involvement of immune escape via the activating receptor. Additionally, NKG2D polymorphisms were also investigated. These data will be combined with MICA results and discussed at the conference.