Expression of immunoglobulin-like transcript (ILT)2 and ILT3 in human gastric cancer and its clinical significance

Abstract

Immune inhibitory receptors play an important role in organ transplantation, autoimmune diseases and cancers. Immunoglobulin-like transcript (ILT)2 and ILT3 belong to the inhibitory receptors of the ILT family, which have been reported to regulate a broad range of cellular functions involved in the immune response. They contain immunoreceptor tyrosine-based inhibitory motifs (ITIMs), which are related to immune regulation. Although ILT receptors have been studied in dendritic cells (DCs), T cells, NK cells and other cell types, the expression and clinical significance of ILT2 and ILT3 in gastric cancer have yet to be elucidated. Here, the expression of ILT2 and ILT3 in gastric cancer cell lines and pathologic tissues, as well as their effects on the cytotoxicity of NK92MI against the gastric cancer cell lines MKNI with ILT2lowILT3low and HGC-27 with ILT2highILT3high were detected. The results suggest that ILT2 and ILT3 are expressed with diverse degrees in gastric cancer cells and tissues, and the expression of ILT2 is related with differentiation and size of tumors. Furthermore, the cytotoxic activity of NK92MI against the MKNI cell line was stronger than that against HGC-27. This study indicates that ILT2 and ILT3 play a key role in gastric cancer immune escape, and ILT2 may be a new target in the clinical diagnosis and treatment of gastric cancer.

Figure 1

Expression of ILT2 and ILT3 mRNA in the gastric cancer cell lines. Expression of ILT2 and ILT3 at the level of mRNA increased with the decreased degree of gastric cancer cell differentiation. ^*P<0.05, ^**P<0.01 by comparision with the well-differentiated gastric cancer cell line (MKN1).

Figure 2

Expression of ILT2 and ILT3 protein in gastric cancer cell lines. The positive rates of ILT2 protein were related to the differentiation of the gastric cancer cells. However, the expression of ILT3 protein did not obviously vary in the gastric cancer cells with different degrees of differentiation. ^*P<0.05, ^**P<0.01 by comparision with the well-differentiated gastric cancer cell line (MKN1).

Figure 3

Killing activity of NK92MI to MKNI and HGC-27 with diverse effector-target ratios. The cytotoxicity of NK92MI to ILT2^lowILT3^low MKNI was stronger than that to ILT2^highILT3^high HGC-27 at different effector-target ratios (except at 1.25:1).

Figure 4

ILT2 and ILT3 immunohistochemical staining of (A and E) poorly differentiated gastric cancer, (B and F) moderately differentiated gastric cancer, (C and G) well-differentiated gastric cancer and (D and H) normal gastric tissue. (Original magnification, ×400) As shown above, ILT2 was expressed in gastric cancer tissues with diverse differentiation degrees and pathologic types, and the expression was correlated with differentiation degrees. Furthermore, there was barely any expression of ILT2 noted in the normal stomach tissue. However, no significantly statistical difference was achieved between ILT3 expression and the differentiation degree and size of the cancer tumors.