title: COX-inhibitors relieve the immunosuppressive effect of tumor cells and improve functions of immune effectors.
abstract: A common phenomenon in cancer patients is a suppressed cell-mediated immunity, characterized by the inability of immune effector cells to mount efficient anti-tumor responses. Immunosuppressive factors, released by the tumor, contribute to this phenomenon and thus to tolerance. Prostaglandins, catalyzed by the cyclooxygenases (COX-1 and COX-2) from arachidonic acid, are one class of these factors. Since at least one of the COX enzymes is often expressed at high level in human cancers, the enzymes were ascribed a causal role in tumor etiology and progression. Non-steroidal antiinflammatory drugs (NSAIDs) like aspirin, which block COX activity, have demonstrated their antitumor effects in preclinical and clinical trials. Pro-apoptotic and anti-angiogenic effects in tumor cells may account for this activity. In addition, by inhibiting the release of prostaglandins from the tumor and by blocking COX activity in immune effector cells, NSAIDs may also bias the function of immune cells towards a more tumoricidal phenotype. We show here that tumor cells inhibit the physiological function of immune cells, and that NSAIDs restore this function. These data contribute to an understanding of the antineoplastic effect ascribed to NSAIDs and support the prophylactic use of these drugs in high-risk patients.
authors.affiliation: Dept. of Otorhinolaryngology, Head and Neck Surgery, University Hospital of Schleswig-Holstein, Luebeck, Germany.
authors.forename: S
authors.initials: S
authors.lastname: Lang
authors.forename: A
authors.initials: A
authors.lastname: Picu
authors.forename: T
authors.initials: T
authors.lastname: Hofmann
authors.forename: M
authors.initials: M
authors.lastname: Andratschke
authors.forename: B
authors.initials: B
authors.lastname: Mack
authors.forename: A
authors.initials: A
authors.lastname: Moosmann
authors.forename: O
authors.initials: O
authors.lastname: Gires
authors.forename: S
authors.initials: S
authors.lastname: Tiwari
authors.forename: R
authors.initials: R
authors.lastname: Zeidler
mesh_terms: D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000494:pharmacology; D001241:Aspirin / Q000494:pharmacology; D017252:CD3 Complex / Q000276:immunology; D002294:Carcinoma, Squamous Cell / Q000276:immunology*; D000068579:Celecoxib; D045744:Cell Line, Tumor; D002478:Cells, Cultured; D018920:Coculture Techniques; D003474:Curcumin / Q000494:pharmacology; D052246:Cyclooxygenase 2 Inhibitors / Q000494:pharmacology; D016861:Cyclooxygenase Inhibitors / Q000494:pharmacology*; D015232:Dinoprostone / Q000096:biosynthesis; D015536:Down-Regulation; D005434:Flow Cytometry; D006258:Head and Neck Neoplasms / Q000276:immunology*; D006801:Humans; D007111:Immunity, Cellular / Q000187:drug effects* / Q000502:physiology*; D007150:Immunohistochemistry; D008264:Macrophages / Q000276:immunology*; D009000:Monocytes / Q000276:immunology*; D011720:Pyrazoles / Q000494:pharmacology; D013347:Subcellular Fractions / Q000276:immunology; D013449:Sulfonamides / Q000494:pharmacology
chemical_list: D000894:Anti-Inflammatory Agents, Non-Steroidal; D017252:CD3 Complex; D052246:Cyclooxygenase 2 Inhibitors; D016861:Cyclooxygenase Inhibitors; D011720:Pyrazoles; D013449:Sulfonamides; D003474:Curcumin; D000068579:Celecoxib; D015232:Dinoprostone; D001241:Aspirin