Recombined CC chemokine ligand 2 into B16 cells induces production of Th2-dominanted cytokines and inhibits melanoma metastasis

This study is aimed to verify whether CCL2 can induce Th2 polarization in vivo and subsequently inhibit tumor metastasis. B16 cells (a murine melanoma cell line) highly expressing CCL2 (CCL2-B16 cells) were obtained by transfection with recombinant plasmid CCL2-pcDNA3. Primary thymocytes were co-cultured with CCL2-B16 cells and STAT-6-mediated Th2 polarization was noticed after co-culture. Caudal vein injection of CCL2-B16 cells effectively inhibited pulmonary metastasis in C57BL/6 mice, but not in nude mice, indicating that T cells play a role in CCL2-induced inhibition of tumor metastasis. We found that high level of CCL2 up-regulated the expression of Th2-related cytokine (IL-4) in tumor microenvironment and increased CD4+, CD8+, and CD45RB+ cells in the peripheral blood and tumor tissues. We also demonstrated that inoculation of mice with CCL2-B16 cells prolonged mice survival time when they were reinjected with wildtype B16 cells, implying that CCL2 can activate immuno-memory in mice. It is concluded that high expression of CCL2 can induce Th2 polarization in tumor microenvironment and can effectively inhibit tumor metastasis, which casts new lights on the role of chemokines in reconstruction of immune surveillance in patients suffering from tumors.