Functional expression cloning identifies COX-2 as a suppressor of antigen-specific cancer immunity

• DOI: 10.1038/cddis.2014.531
• Publication Date: 2014-12-11T13:54:48Z
• Authors: C Göbel; F Breitenbuecher; H Kalkavan; P S Hähnel; S Kasper; S Hoffarth; K Merches; H Schild; K S Lang; M Schuler
• Keywords: Cloning (programming)

Abstract The efficacy of immune surveillance and antigen-specific cancer immunotherapy equally depends on the activation a sustained response targeting antigens susceptibility cells to effector mechanisms. Using functional expression cloning T-cell receptor (TCR) transgenic mice, we have identified cyclooxygenase 2/prostaglandin-endoperoxide synthase 2 (COX-2) as resistance factor against cytotoxicity induced by activated, T cells. Expressing COX-2, but not catalytically inactive COX-2 mutant, increased clonogenic survival E1A-transformed murine when cocultured with lymphocytes from St42Rag2 −/− mice harboring TCR directed an E1A epitope. expressing tumors established in immune-deficient were less susceptible adoptive vivo . Also, COX-2-positive tumor was efficient. growth MC-GP tumors, which show high endogenous expression, immunocompetent effectively suppressed treatment selective inhibitor, celecoxib. Mechanistically, blunted interferon-gamma release exposed their respective cellular targets, interleukin-4 indoleamine 2,3-dioxygenase Addition sensitized suppression In conclusion, is frequently colorectal cancer, contributes evasion local functions.