The Role of Chemokines CCL19b and CCL25b in T Cell Recruitment Into Melanoma Tumors.

Abstract

Malignant melanoma is an extremely metastatic cancer that is highly resistant to conventional therapy. One of the developing approaches to address melanoma involves immunotherapy. Immunotherapy involves harnessing the immune system to fight cancer. One of the major problems in melanoma immunotherapy is the inadequate migration of T cells to the tumor and proper tumor recognition. The aim of this study is to improve T cell recruitment to melanoma using zebrafish as a model organisms. Chemokine CCL19 is important for migration of antigen-presenting cells and lymphocytes into the lymph node. CCL25 is involved in the localization of recently activated CD8+ lymphocytes. We hypothesized that induced expression of CCL19 and CCL25 increases T cell recruitment into melanoma tumors. Here, we developed melanoma cell lines with chemokine overexpression and transplanted these into zebrafish. Tumors were excised 2, 3, and 4 weeks post-transplantation and processed through FACS to analyze T cell recruitment. Results showed that induced expression of CCL19 provided a slight elevation of T cells lasting 2 weeks, while CCL25 provided a greater elevation of T cells lasting 3 weeks. Our observation that induced expression of chemokines CCL25 increases T cell recruitment may present an new option to supplement other immunotherapies.