Secondary lymphoid tissue chemokine mediates T cell-dependent antitumor responses in vivo

Secondary lymphoid tissue chemokine (SLC, also referred to as Exodus 2 or 6 Ckine) is a recently identified high endothelial-derived CC chemokine, The ability of SLC to chemoattract both Th1 lymphocytes and dendritic cells for med the rationale to evaluate this chemokine in cancer immunotherapy, Intra tumoral injection of recombinant SLC evidenced potent antitumor responses a nd led to complete tumor eradication in 40% of treated mice. SLC-mediated a ntitumor responses were lymphocyte dependent as evidenced by the fact that this therapy did not alter tumor growth in SCID mice. Studies performed in CD4 and CD8 knockout mice also revealed a requirement for both CD4 and CD8 lymphocyte subsets for SLC-mediated tumor regression. In immunocompetent mi ce, intratumoral SLC injection led to a significant increase in CD4 and CD8 T lymphocytes and dendritic cells, infiltrating both the tumor and the dra ining lymph nodes. These cell infiltrates were accompanied by the enhanced elaboration of Th1 cytokines and chemokines monokine induced by IFN-gamma a nd IFN-gamma-inducible protein 10 but a concomitant decrease in immunosuppr essive cytokines at the tumor site. In response to irradiated autologous tu mor, splenic and lymph node-derived cells from SLC-treated tumor-bearing mi ce secreted significantly more IFN-gamma, GM-CSF, and IL-12 and reduced lev els of IL-10 than did diluent-treated tumor-bearing mice. After stimulation with irradiated autologous tumor, lymph node-derived lymphocytes from SLC- treated tumor-bearing mice demonstrated enhanced cytolytic capacity, sugges ting the generation of systemic immune responses. These findings provide a strong rationale for further evaluation of SLC in tumor immunity and its us e in cancer immunotherapy, The Journal of Immunology, 2000, 164: 4558-4563.