title: Sulindac, a non-steroidal anti-inflammatory drug, mediates breast cancer inhibition as an immune modulator.
abstract: The cooperation of adaptive immunity with pharmacologic therapy influences cancer progression. Though non-steroidal anti-inflammatory drugs (NSAIDs) have a long history of cancer prevention, it is unclear whether adaptive immune system affects the action of those drugs. In present study, we revealed a novel immunological mechanism of sulindac. Our data showed that sulindac had substantial efficacy as a single agent against 4T1 murine breast cancer and prolonged the survival of tumor-bearing mice. However, in the athymic nude mice, sulindac treatment was ineffective. Further in vivo T cell subsets depletion experiments showed that CD8+ T lymphocytes deficiency reversed the anti-tumor effect of sulindac. In addition, sulindac significantly reduced M2 macrophages recruitment, cancer-related inflammation and tumor angiogenesis. Our results advance our understanding of the mechanisms of NSAIDs, and more importantly, this will provide insight into rational drug design or antitumor immunotherapy.
authors.affiliation: State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, Sichuan University, and Collaborative Innovation Center of Biotherapy, Chengdu 610041, PR China.
authors.forename: Tao
authors.initials: T
authors.lastname: Yin
authors.affiliation: State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, Sichuan University, and Collaborative Innovation Center of Biotherapy, Chengdu 610041, PR China.
authors.forename: Guoping
authors.initials: G
authors.lastname: Wang
authors.affiliation: State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, Sichuan University, and Collaborative Innovation Center of Biotherapy, Chengdu 610041, PR China.
authors.forename: Tinghong
authors.initials: T
authors.lastname: Ye
authors.affiliation: State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, Sichuan University, and Collaborative Innovation Center of Biotherapy, Chengdu 610041, PR China.
authors.forename: Yongsheng
authors.initials: Y
authors.lastname: Wang
mesh_terms: D056704:Adaptive Immunity / Q000187:drug effects; D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000494:pharmacology*; D001943:Breast Neoplasms / Q000188:drug therapy / Q000276:immunology* / Q000401:mortality / Q000473:pathology*; D045744:Cell Line, Tumor; D016207:Cytokines / Q000378:metabolism; D004195:Disease Models, Animal; D006801:Humans; D007155:Immunologic Factors / Q000494:pharmacology*; D056747:Immunomodulation / Q000187:drug effects*; D018836:Inflammation Mediators / Q000378:metabolism; D008212:Lymphocyte Depletion; D008264:Macrophages / Q000187:drug effects / Q000276:immunology / Q000378:metabolism; D051379:Mice; D009362:Neoplasm Metastasis; D009389:Neovascularization, Pathologic; D013467:Sulindac / Q000494:pharmacology*; D016176:T-Lymphocyte Subsets / Q000187:drug effects / Q000276:immunology / Q000378:metabolism; D047368:Tumor Burden / Q000187:drug effects / Q000276:immunology; D059016:Tumor Microenvironment / Q000187:drug effects / Q000276:immunology
chemical_list: D000894:Anti-Inflammatory Agents, Non-Steroidal; D016207:Cytokines; D007155:Immunologic Factors; D018836:Inflammation Mediators; D013467:Sulindac