Abstract

In previous studies, the chemokine CCL21 has shown biological activities that include T cell, natural killer (NK) cell, and dendritic cell (DC) chemoattraction. The goal of this study was to determine the effects of administering CCL21 to orthotopic mammary tumors in terms of impact on tumor growth rate, immune cell infiltration of the primary tumor, and survival. We found that a single intratumoral administration of CCL21 slowed the growth of orthotopic mammary tumors and increased intratumoral infiltration by T cells, NK cells, and DCs. CCL21 intratumoral administration also prolonged the survival of tumor-bearing mice. Furthermore, mice that received intratumoral neoadjuvant CCL21 prior to surgical resection of tumors survived significantly longer than control mice. The surviving neoadjuvant CCL21-treated mice, when challenged again with cl-66, had a significantly slower rate of tumor growth than challenged control mice. Thus, our data indicate that CCL21 treatment prior to mammary tumor resection can significantly prolong survival and increase resistance to subsequent tumor challenge. Overall, our findings suggest that intratumoral administration of CCL21 has potential as a neoadjuvant immunotherapy for breast cancer.

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