Inflammatory chemokine CCL3 Leads to enhanced antitumor development in the draining lymph node (TUM10P.1053)

CCL3 has been shown to be important in orchestrating cellular contacts in vaccinated lymph nodes. Moreover, dendritic cells can mediate both tumor tolerance and anti-tumor immunity in some tumor models. We hypothesize that incorporating CCL3 into tumor vaccines can enhance anti-tumor immunity. We inoculated naive recipient mice with either WT or CCL3-secreting colon tumors. CCL3-secreting tumors showed enhanced antitumor immunity and suppressed growth kinetics in immunocompetent mice versus WT-tumors. Relative to non-injected controls or WT-injected tumors, 3 days after injections CCL3-secreting tumors revealed an increase of CD4 + , CD8 + , and CD19 + lymphocyte in the draining lymph node. Concurrently we conducted in vitro BMDCs experiments to assess the effects the tumor microenvironment (+/- CCL3) has on the capacity of DCs to upregulate T cell activation and adhesion molecules. BMDCs differentiated in the presence of CCL3 showed a greater capacity to upregulation CD86, ICAM1, CD11b, and CCR7 before and after LPS stimulation. Moreover, BMDCs cultured in the presence of WT and CCL3-secreting tumor supernatants revealed an increase in CD86, MHCII, and CCR7 before and after LPS stimulation. Together these data reveal that CCL3 in the tumor microenvironments leads to a reduction in tumor growth and early lymphocyte accumulation in the DLN, which may be a result of an enhanced capacity for DCs to home to the DLN and activate antitumor T cells.