title: CD137 agonist antibody prevents cancer recurrence: contribution of CD137 on both hematopoietic and nonhematopoietic cells.
abstract: Antigen-specific memory T cells (Tms) are essential in the immune surveillance of residual and metastatic tumors. Activation of Tms requires designing vaccines based on tumor rejection antigens, which are often not available to cancer patients. Therefore, it is desirable to have a general applicable approach to activate Tms without extensive knowledge of tumor antigens. Here, we report that activation of antigen-specific Tms could be achieved by the administration of agonistic anti-CD137 monoclonal antibody without additional tumor vaccination, leading to the prevention of recurrence and metastases after surgical resection of primary tumors in mouse models. By reconstitution with CD137-deficient Tms, we demonstrate that expression of CD137 on antigen-specific Tms is only partially required for the effect of anti-CD137 antibody. Other host cells, including those from hematopoietic and nonhematopoietic origins, are also important because ablation of CD137 from these cells partially but significantly eliminates antitumor effect of anti-CD137 antibody. Our findings implicate a potential new approach to prevent recurrence and metastases in cancer patients.
authors.affiliation: Department of Oncology and the Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
authors.forename: Hidehiko
authors.initials: H
authors.lastname: Narazaki
authors.forename: Yuwen
authors.initials: Y
authors.lastname: Zhu
authors.forename: Liqun
authors.initials: L
authors.lastname: Luo
authors.forename: Gefeng
authors.initials: G
authors.lastname: Zhu
authors.forename: Lieping
authors.initials: L
authors.lastname: Chen
mesh_terms: D000818:Animals; D000911:Antibodies, Monoclonal / Q000627:therapeutic use*; D019496:Cancer Vaccines / Q000627:therapeutic use; D002478:Cells, Cultured; D005260:Female; D006412:Hematopoietic Stem Cells / Q000378:metabolism; D007156:Immunologic Memory / Q000276:immunology; D008546:Melanoma, Experimental / Q000276:immunology / Q000473:pathology / Q000628:therapy; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D008811:Mice, Inbred DBA; D008822:Mice, Transgenic; D009362:Neoplasm Metastasis; D009369:Neoplasms / Q000276:immunology / Q000401:mortality / Q000473:pathology / Q000517:prevention & control*; D055502:Secondary Prevention; D016019:Survival Analysis; D050378:T-Lymphocytes, Regulatory / Q000276:immunology / Q000473:pathology / Q000502:physiology; D053261:Tumor Necrosis Factor Receptor Superfamily, Member 9 / Q000819:agonists* / Q000276:immunology / Q000378:metabolism / Q000502:physiology*
chemical_list: D000911:Antibodies, Monoclonal; D019496:Cancer Vaccines; D053261:Tumor Necrosis Factor Receptor Superfamily, Member 9