Impaired monocyte function in cancer patients: restoration with a cyclooxygenase-2 inhibitor

SPECIFIC AIMSCarcinoma patients suffer from a tumor-suppressed immune system. This phenomenon is attributable to the tumor itself, which produces and secretes immunosuppressive factors such as prostaglandin E2 (PG), known to be elevated in cancer patients. Cyclooxygenase (COX) inhibitors that block PG synthesis demonstrated remarkable anti-cancer effects. Evidence has accumulated showing that inhibition of COX-2 plays a key role in suppressing multistep carcinogenesis. However, the exact mechanism as to how NSAIDs prevent cancer is still unclear.PRINCIPAL FINDINGS1. CCR5 expression is reduced on monocytes isolated from tumor patientsProper expression of chemokine receptors is a pivotal prerequisite for the extravasation of monocytes, and thus for physiological function. We recently demonstrated that the chemokine receptor CCR5 is down-regulated on monocytes after incubation of these cells in PG-containing supernatants from carcinoma cell lines. We have also shown that this receptor was not down-regulated ...