ICAM-1 Enhances NKG2D-mediated Killing Of Colorectal Cancer Cells By NK Cells

Colorectal cancer(colorectal cancer,CRC)is the most common malignant tumors in addition to lung cancer and breast cancer and has caused serious threats to human health.More than one million men and women are affected each year in the world and more than half of the patients die.Accourding to the latest statistics,CRC is the third malignant tumor in men and women in 2017.The use of the immune system for cancer treatment has become a very promising way for patients in addition to surgical treatment,the development of new chemotherapy drugs and improves the radiotherapy methods;Tumor immunotherapy for CRC patients may be more effective in inhibiting tumor progression and preventing recurrence.NK cells are lymphocyte populations with rapid cytotoxic effects,and NK cells can act as effector cells for adoptive immunotherapy due to their unique biological properties.The killing ability of NK cells was closely controlled by the activation and inhibitory signal.The achievement of the balance between inhibition and activation signal is really important for NK cell response in the microenvironment of the tumor.NKG2 D is a C-type lectin-like transmembrane-activated receptor,expressed on natural killer and other killer immune cells.It is the main receptor for NK cells to recognize target cells.NKG2 D is one of the most widely studied immune cell receptors because of it can activate NK cells and act its anti-infective anti-tumor function.The expression of NKG2 D can be regulated by different regulatory mechanisms.A kill-dependent regulatory network controls NKG2D-dependent antitumor immunity.Intercellular adhesion molecule-1(ICAM-1)belongs to the adhesion molecule immunoglobulin superfamily(Ig SF),through the mediated cell-cell,cell-extracellular matrix adhesion between the body involved in many inflammatory reactions and immune response process.ICAM-1 is the most widely studied molecule in the ICAM family and is a membrane-bound glycoprotein of the immunoglobulin(Ig)superfamily.The expression of ICAM-1 may affect the ability of NK cells to bind to osteosarcoma cells.ICAM-1 plays an important role in the sensitivity of NK cells to tumor cells.Further studies have shown that the up-regulation of ICAM-1 expression in target cells can increase the target cells sensitivity to NK cells.Similarly,down-regulation of ICAM-1 expression by resistance to NK cell killing,the apoptosis of tumor cells was significantly reduced in prostate cancer.Overexpression of ICAM-1 on the surface of the insect cells model can improve the adhesion of NK cells,while NK cells tend to differentiate into cells with killing effect and kill the target cells.At the same time,ICAM-1 can also affect the polarization of mononuclear cells.Thus we speculate that ICAM-1 plays an important role in NK cell killing of tumor cells.In this study,we investigated the possible involvement of ICAM-1 in tumor progression in CRC and elucidated some of its molecular mechanisms that affect tumor progression.We found that ICAM-1 can promote NK cell killing tumor cells in vitro and in vivo,and determined that ICAM-1 can promote the expression of NKG2 D ligand on the surface of tumor cells and further promote NKG2 D expression in NK cell,thus promoting NK cells to kill tumor cells.This study provides a theoretical basis for clinically research in increasing the activity of NK cells,thus providing a choice for CRC immunotherapy.