Secondary lymphoid organ chemokine reduces pulmonary tumor burden in spontaneous murine bronchoalveolar cell carcinoma

The antitumor efficiency of secondary lymphoid organ chemokine (SLC), a CC chemokine that chemoattracts both dendritic cells (DCs) and T lymphocytes, was evaluated in SV40 large T-antigen transgenic mice that develop bilatera l multifocal pulmonary adenocarcinomas. Injection of recombinant SLC in the axillary lymph node region led to a marked reduction in tumor burden with extensive lymphocytic and DC infiltration of the tumors and enhanced surviv al. SLC injection led to significant increases in CD4 and CD8 lymphocytes a s well as DC at the tumor sites, lymph nodes, and spleen. The cellular infi ltrates were accompanied by the enhanced elaboration of Type 1 cytokines an d the antiangiogenic chemokines IFN-gamma inducible protein 10, and monokin e induced by IFN-gamma (MIG). In contrast, lymph node and tumor site produc tion of the immunosuppressive cytokine transforming growth factor beta was decreased in response to SLC treatment. In vitro, after stimulation with ir radiated autologous tumor, splenocytes from SLC-treated mice secreted signi ficantly more IFN-gamma and granulocyte macrophage colony-stimulating facto r, but reduced levels of interleukin 10. Significant reduction in tumor bur den in a model in which tumors develop in an organ-specific manner provides a strong rationale for additional evaluation of SLC in regulation of tumor immunity and its use in lung cancer immunotherapy.