Abstract: Compositions and methods are provided for suppressing tumors by modulating the LAP pathway. Targeting components of the LAP pathway for specific drug design can be used as n immunotherapy strategy that modulates the tumor microenvironment. It is well established that infiltrating monocytes and macrophages play a pivotal role in shaping an immunosuppressive tumor microenvironment. By modulating LAP in the innate immune cells, the function of effector T cells can be manipulated toward an effective, cytotoxic immune response that can eliminate tumor cells. Thus, methods are provided for reducing the size or number of tumor cells and for treating cancer or other cell proliferative disorders. Further provided are methods for increasing the Th1 response or increasing IFN? and/or TNF? expression in the tumor microenvironment by administering a LAP inhibitor.

Abstract: Compositions and methods are provided for suppressing tumors by modulating the LAP pathway. Targeting components of the LAP pathway for specific drug design can be used as n immunotherapy strategy that modulates the tumor microenvironment. It is well established that infiltrating monocytes and macrophages play a pivotal role in shaping an immunosuppressive tumor microenvironment. By modulating LAP in the innate immune cells, the function of effector T cells can be manipulated toward an effective, cytotoxic immune response that can eliminate tumor cells. Thus, methods are provided for reducing the size or number of tumor cells and for treating cancer or other cell proliferative disorders. Further provided are methods for increasing the Th1 response or increasing IFN? and/or TNF? expression in the tumor microenvironment by administering a LAP inhibitor.

Abstract: Compositions and methods are provided for blocking Tim4 on the surface of myeloid cells in order to treat and prevent cancer in a subject. Blocking Tim4 on the surface of myeloid cells can restore anti-tumor immunity and reduce the uptake of apoptotic cells. Further, by administering an anti-Tim4 antibody, the pro-inflammatory anti-tumor response can be increased. Accordingly, methods for reducing the uptake of apoptotic cells and methods for increasing anti-tumor immunity are provided herein. The present disclosure further describes a method for producing monoclonal antibodies that bind Tim4 on the surface of myeloid cells. The anti-Tim4 antibodies can further be selected for their ability to inhibit engulfment of dead or dying cells, to elicit the production of inflammatory cytokines, and to restrict the growth of tumors.