Abstract
BackgroundSLC/CCL21, normally expressed in high endothelial venules and in T cell zones of spleen and lymph nodes, strongly attracts T cells and dendritic cells (DC). We have previously shown that SLC/CCL21-mediated anti-tumor responses are accompanied by significant induction of IFNγ and the CXC chemokines, monokine induced by IFNγ (MIG/CXCL9) and IFNγ-inducible protein-10 (IP-10/CXCL10).ResultsWe assessed the importance of IFNγ, IP-10/CXCL10 and MIG/CXCL9 in SLC/CCL21 therapy. In vivo depletion of IP-10/CXCL10, MIG/CXCL9 or IFNγ significantly reduced the anti-tumor efficacy of SLC/CCL21. Assessment of cytokine production at the tumor site showed an interdependence of IFNγ, MIG/CXCL9 and IP-10/CXCL10; neutralization of any one of these cytokines caused a concomitant decrease in all three cytokines. Similarly, neutralization of any one of these cytokines led to a decrease in the frequency of CXCR3+ve T cells and CD11c+ve DC at the tumor site.ConclusionThese findings indicate that the full potency of SLC/CCL21-mediated anti-tumor responses require in part the induction of IFNγ, MIG/CXCL9 and IP-10/CXCL10.
Highlights
SLC/CCL21, normally expressed in high endothelial venules and in T cell zones of spleen and lymph nodes, strongly attracts T cells and dendritic cells (DC)
Antibodies to: IP-10/CXCL10, MIG/CXCL9 and IFNγ significantly inhibited the antitumor efficacy of SLC/CCL21 (*p < 0.01 compared to the control antibody treated group). n = 8 mice group that attract host antigen presenting cells (APC) and T cells could serve as potent agents for cancer immunotherapy
Neutralization of any one of these cytokines caused a concomitant decrease in all three cytokines, indicating that IFNγ, MIG/CXCL9 and IP-10/CXCL10 are interdependent in the SLC/CCL21-mediated anti-tumor responses
Summary
We assessed the importance of IFNγ, IP-10/CXCL10 and MIG/CXCL9 in SLC/CCL21 therapy. In vivo depletion of IP-10/CXCL10, MIG/CXCL9 or IFNγ significantly reduced the antitumor efficacy of SLC/CCL21. Assessment of cytokine production at the tumor site showed an interdependence of IFNγ, MIG/CXCL9 and IP-10/CXCL10; neutralization of any one of these cytokines caused a concomitant decrease in all three cytokines. Neutralization of any one of these cytokines led to a decrease in the frequency of CXCR3+ve T cells and CD11c+ve DC at the tumor site
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