Hematopoietic expression of CXCR3 is required for melanoma engraftment of lung (TUM7P.936)

• Published in: The Journal of immunology (1950) 2014-05, Vol.192 (1_Supplement), p.203-203.18
• Main Authors: Clancy-Thompson, Eleanor, Mullins, David
• Format: Article
• Language: English
• ISSN: 0022-1767; 1550-6606
• DOI: 10.4049/jimmunol.192.Supp.203.18

Chemokine receptors have an established role in immune cell trafficking, and a less well-defined role in metastasis. Recent literature has demonstrated a role for tumor-expressed CXC chemokine receptor 3 (CXCR3) in metastasis to lymph nodes, but no study has evaluated the role of host CXCR3 expression in melanoma metastasis. To assess this possibility, we injected B16 melanoma intravenously into CXCR3wt or CXCR3-/- mice and assayed for melanoma-specific gene expression (tyrosinase) 24 hours later. Gene expression was significantly (9.5-fold) higher in CXCR3wt mice. At 24h, this is likely due to differential engraftment of the melanoma in the lung, as opposed to different growth. To determine if the CXCR3-expressing host contribution is an immune component, we phenotyped cells in the lungs 24 hours after melanoma injection. Neutrophils, CD8+ T cells, and B cells were significantly increased in CXCR3-/- mice versus CXCR3wt mice after melanoma injection, whereas macrophages/DCs, CD4+ T cells, and NK cells were not significantly different. Using bone marrow chimeras, we have shown that melanoma engraftment in the lungs requires a host CXCR3-expressing cell of the hematopoietic cell lineage. A role for host CXCR3-expressing cells to mediate melanoma engraftment in the lungs has not been previously shown, and these studies may predict future targets for the reduction or prevention of melanoma metastases in patients.