Modification of chemokine receptor expression to enhance levels of trafficking receptors on autologous cytokine-induced killer cells derived from patients with colorectal cancer

Abstract

Cytokine-induced killer (CIK) cells have achieved therapeutic benefit in treatment of solid tumors in clinic. However, some patients show no response after CIK treatment. Animal assays have shown that successful infiltration of CIK cells to the tumor sites could affect the outcome. Chemokines play important roles in lymphocyte trafficking. Understanding the molecular mechanism of chemokines in the process of CIK cell homing is important for further modification of CIK therapy. In this study, we investigated the spectrum of chemokine ligands in the colorectal cancer sites and observed that chemokine ligands CCL20 and CXCL10 were overexpressed in the CRC tumor tissues compared with adjacent tissues. Although the corresponding receptors CCR6 and CXCR3 increased on CIK cells compared with PBMCs, their expression on CIK cells derived from CRC patients had lower levels than healthy donors, which might be a limited factor for autologous-CIK cells trafficking to tumor site. Importantly, stimulation with chemokines CCL20 and CXCL10 promotes the expression levels of CCR6 and CXCR3 on CIK cells, thus augmenting the relative migration of CIK cells in vitro. Our results suggest that modification of surface chemokine receptors may enhance the homing ability of CIK cells for better therapeutic achievements.