A study on crosstalk between lung carcinoma and immune cells

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