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-Ξ±, IL-6, IL-10, IL-12p40 but not IL-12p70
or IL-1Ξ² 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