A study on crosstalk between lung carcinoma and immune cells

Abstract

newlineTumor cells are seen to modulate the phenotype of all major immune cells to newlineexpress tumor favouring phenotypes. Inflammation associated with tumors, a result of newlinesuch interaction, is increasingly being believed to play a major role in tumor initiation, newlineprogression and even metastasis. This modulation is achieved very early when newlineMonocytes, precursors of Macrophages and DCs, from the circulating pool are recruited newlinetowards tumors and selectively differentiated. Monocytes, in particular, are thought to newlinegenerate a cytokine milieu in the microenvironment favourable to tumor. Such a newlinecrosstalk and the pathways involved therein are not well established, especially in human newlinemodels. Using representative human carcinoma cells of different origin including Lung, newlineColon and Cervix, we show that factor(s) associated with these cells can activate newlinesecretion of tumor-associated cytokines, TNF-and#945;, IL-6, IL-10, IL-12p40 but not IL-12p70 newlineor IL-1and#946; from human monocytes. Comparative murine co-cultures are also able to induce newlinesimilar responses. Treatment of monocytes with TLR-2 blocking antibody inhibits these newlineinflammatory responses upon encountering cell-associated as well as secretory ligand(s) newlinefrom tumor cells. Pharmacological inhibition of intracellular MAP kinase pathway in newlinecarcinoma cells ablates the TLR-2 agonistic activity of carcinoma cells. However, newlineinhibition of EGFR and Ras, two major oncogenic players, had no such effect. Early newlineinflammatory response tends to enhance the proliferation and invasiveness of tumor cells newlineand concurrently, increase the viability of monocytes. These tumor associated newlineinflammatory responses may well be one of the mechanisms to manipulate effector T-cell newlineresponse against tumors. These results suggest a previously unrecognized pathway that newlinemay regulate inflammatory responses triggered by cancer cells from monocytes. Our newlinefindings have important implications for understanding Cancer related Inflammation.