Evaluation of myeloid cell suppression related to cancer cell released products (TUM4P.913)

Abstract

Abstract Dendritic cells (DCs) and macrophages may recognize tumor antigens and initiate an antitumoral response before and after the formation of tumor mass. However, the secretion of cytokines and factors that inhibit myeloid cells is a mechanism used by tumor cells to escape from immune attack. Our aim was to understand how tumor cells modulate the generation of murine macrophages and human DCs. For this, we collected bone marrow cells from C57Bl/6 mice and differentiated with M-CSF in the presence of 3LL (Lewis lung carcinoma) or MN/MCA (fibrosarcoma) supernatants. Some cells were activated with IFN-γ and LPS to obtain M1 macrophages or IL-4 to M2. Data showed increased expression of arginase-1 mRNA in macrophages differentiated with MN/MCA supernatant and it happened both in M1 and M2. About 20% of cells proliferate in the presence of supernatants, even in the absence of M-CSF and they express higher level of CD16. Moreover, we differentiated human DCs from monocytes with IL-4 and GM-CSF in the presence of K562 (chronic myeloid leukemia) supernatants. TNF-α was added to activate the cells. It was observed higher percentage of cells expressing CD80 when the differentiation was done with K562 supernatant. Higher secretion of IL-10 and lower production of IL-12 were found in cells differentiated with K562 supernatant and later activated. Therefore, the development and function of macrophages and DCs are affected by tumor products and both cells present some suppressive features.