Antitumor effects of the mouse chemokine 6Ckine/SLC through angiostatic and immunological mechanisms

Mouse 6Ckine/SLC (secondary lymphoid tissue chemokine) is a chemotactic fac tor for dendritic cells, T cells, and NR cells in vitro. In addition, mouse 6Ckine/SLC interacts with the chemokine receptor CXCR3, as do several chem okines with antiangiogenic properties. These dual properties of mouse 6Ckin e/SLC were tested for the induction of an antitumor response by transducing the C26 colon carcinoma tumor cell line with a cDNA encoding mouse 6Ckine/ SLC, The C26-6CK-transduced cells showed reduced tumorigenicity in immunoco mpetent or in nude mice, Part of this effect was likely due to angiostatic mechanisms as shown by immunohistochemistry and Matrigel assay. C26-6CK tum ors were also heavily infiltrated with leukocytes, including granulocytes, dendritic cells, and CD8(+) T cells. In vivo, anti-CDS treatment increased the tumorigenicity of the C26-6CK tumor cells, and tumor-infiltrating CD8() T cells had the phenotype of memory effector cells, suggesting the induct ion of cytotoxic tumor-specific T lymphocytes, On the other hand, anti-asia lo-G(M1) depletion also increased the tumorigenicity of C26-6CK cells, supp orting the participation of NK cells. Finally, tumor-infiltrating dendritic cells had the phenotype and functional features of Immature dendritic cell s. Overall, these results suggest that mouse 6Ckine/SLC has strong antitumo r effects by inducing both angiostatic, CD8(+) T cell-mediated, and possibl y NK-mediated tumor resistance mechanisms.