Lenalidomide Role Of Tumor-associated Macrophage Cells And Its Effect On The Growth Of Lymphoma

Background:Lymphoma is a relatively rare malignant tumor, and some subtypes are currently lack of effective treatment and poor prognosis. Therefore it is important to find potential therapeutic targets, and to study of anticancer drugs. Recent studies found that Tumor-Associated Macrophages (TAMs) is a very important part of the tumor microenvironment. It has a strong plasticity, and plays an important role in the process of tumor progression and metastasis. And also it is one of adverse prognostic factors for lymphoma. Anticancer drugs lenalidomide is expected to affect the TAMs in the tumor microenvironment by immune regulatory effects, and in order to play the role of anti-tumor.Objective:Study the conversion of monocytes and TAMs in the tumor microenvironment and the effect of TAMs to growth of lymphoma cells by the co-culture modle of human mononuclear cells and lymphoma cells in vitro. Study the immunomodulatory effects of lenalidomide to TAMs, and result of these effects by the co-culture modle of human mononuclear cells and lymphoma cells in vitro.Methods:This study involved13patients and7healthy volunteers. After get the blood mononuclear cells of thess people, co-culture these mononuclear cells with the lymphoma cell lines called HUT-78. Make growth curve of lymphoma cells in each group, Use the flow cytometry to detecte the expressions of CD14, CD68and CD163on sueface of the monocytes of each group before and after cell culture. SPSS is used to analyze every subject of lymphoma cell growth curve and the change of CD14, CD68, of CD163phenotypes.Results:1. In the co-culture model, when lymphoma cells co-culture with patients’ mononuclear cells, its growth is significantly better than the lymphoma cells cultured alone (P<0.05); when lymphoma cells co-culture with patients’ negative cells (ie, monocytes free, other cellular components of mononuclear cells), the growth of lymphoma cells is no different with lymphoma cells cultured alone (P>0.05); when lymphoma cells co-culture with healthy volunteers’ mononuclear cells, the growth of lymphoma cell is changeable.2. The lenalidomide may have some inhibitory effects on the growth of lymphoma cells cultured alone, and after the statistical analysis only some of the growth curves has differences (P<0.05).3. In the co-culture model, the growth of lymphoma cells are inhibited significantly (P <0.05) in the use of lenalidomide.4. In the co-culture model, the proportion of patients’monocytes of CD68+, of CD163+and of CD68+CD163+significantly increase (P<0.05) after the co-culture; the proportion of healthy volunteers of CD68+, of CD163+and of CD68+CD163+cells decline after the co-culture, and there is no significant difference (P>0.05).5. In the co-culture model, the proportion of patients’mononuclears of CD68+, of CD163+and of CD68+CD163+significantly reduce (P<0.05) after the use of lenalidomide; while the proportion of healthy volunteers’ mononuclears of CD68+and of CD163+have no significant change (P>0.05) after using lenalidomide, percentage of CD68+CD163+cell has decreased, but no significant (P=0.075).Conclusion:The tumor microenvironment provided by the lymphoma cells may act on patients’ mononuclear cells, and promote the conversion to the TAMs. And TAMs from monocytes can facilitate the growth of lymphoma cells. Lenalidomide may inhibit the growth of lymphoma cells. And Lenalidomide act on TAM cells as targets, to further play the role of inhibition of lymphoma cell growth by inhibiting the conversion of TAMs. Mononuclear cells of healthy volunteers and patients may be different, which may affect the effect of the conversion of the monocytes to TAMs, and caused a series of follow-up effects.