Regulation of CXCR3 chemokine production and CD8+ T cell infiltration in the metastatic melanoma microenvironment (P5091)

• Published in: The Journal of immunology (1950) 2013-05, Vol.190 (1_Supplement), p.129-129.10
• Main Authors: Clancy-Thompson, Eleanor, Mullins, David
• Format: Article
• Language: English
• ISSN: 0022-1767; 1550-6606
• DOI: 10.4049/jimmunol.190.Supp.129.10

Vaccine-based immune therapy has shown minimal efficacy against established tumors. However, vaccination in the adjuvant setting prolongs disease-free survival. We previously demonstrated that CXCR3 expression by tumor antigen-specific T cells correlates with this. We hypothesized that melanoma engraftment may induce spatially- and temporally-restricted expression of CXCR3 chemokines in the tumor microenvironment, leading to transient infiltration of CXCR3+ T cells into tumor. We used a model of murine metastatic-like melanoma to evaluate tyrosinase expression as a measure of tumor burden. We observed a positive correlation between tyrosinase and CXCL9 (r2 = 0.73) and CXCL10 (r2 = 0.86) expression over time, demonstrating that melanoma growth in the lung is sufficient to induce CXCR3-cognate chemokines. In a time-course study, we observed that CXCL9 and CXCL10 expression decrease after day 15; we hypothesize that diminished chemokine production is due to reduced interferon signaling. We are investigating this possibility. Our preliminary flow cytometry analyses suggest a positive correlation between CD8+ T cell infiltration and the expression of CXCL9/10, suggesting that metastatic melanomas are transiently receptive to T cell infiltration. Therefore, successful immunotherapy of metastatic melanoma may require adjuvant therapy to induce or extend the chemotactic window for T cell infiltration.