304 Myeloid response and macrophage polarization in mouse melanoma lung metastasis

Myeloid derived cells contribute to tumour growth by suppressing immune responses and providing the tumour cells with inflammatory cytokines. Monocytes acquire different functional traits during polarization to the classical pro-inflammatory M1 or the alternative anti-inflammatory/pro-tumoural M2macrophage. The macrophage mannose receptor (MR) has been found upregulated in the M2 phenotype and has been shown to be essential for cytokine production. MR might also interact with other canonical pattern recognition receptors in order to mediate intracellular signalling. In an experimental model of mouse melanoma lung metastasis, we aim to describe the recruitment of myeloid cells into the lung after tumour cell challenge in a time dependent manner. Twenty-four hours after injection ofB16F10 cells into the tail vein of C57BL/6 mice we observed a marked infiltration of CD68+CD11b+CD11c− monocytes into the lung. A fraction of these monocytes was Gr-1+. The infiltration ceased within 48 h. In C57BL/6mice lacking MR (MR−/−), recruitment of these monocytes was abrogated. Three weeks after tumour cell injection, fewer lung colonies were scored in the MR−/− than in the wild type mice, suggesting a possible role for MR both in early and late stages of metastasis formation. We aim to further characterize the monocyte and macrophage populations involved in lung colony formation with particular interest in the expression of macrophage polarization-related genes. We are using PCR arrays on monocytes and macrophages sorted from the mouse lungs following tumour cell challenge. The candidate polarization genes as potential targets in melanoma lung metastasis will be discussed.