Abstract: Antibodies or antigen binding fragments thereof that bind HVEM, inhibit HVEM-BTLA interaction and allow binding to LIGHT are provided. Methods of treating disease with these antibodies or antigen binding fragments thereof, nucleic acid molecules encoding these antibodies or antigen binding fragments thereof and kits comprising these antibodies or antigen binding fragments thereof are also provided.

Abstract: Methods of treating, preventing or ameliorating cancer by decreasing Ephrin type-B receptor 2 (EPHB2) function in a cancer cell and administering an immunotherapy are provided. Methods of enhancing an immunotherapy by decreasing EPHB2 function are also provided. Antibodies, pharmaceutical compositions and kits for performing the methods of the invention, and methods of producing those antibodies are also provided.

Abstract: Methods of determining suitability of a subject to be treated with a PD-1/PD-L1 based immunotherapy, comprising receiving a sample from the subject and determining HVEM levels in the sample, wherein expression of HVEM above a predetermined threshold indicates the subject is suitable to be treated by the immunotherapy or of determining suitability of a subject non-responsive to a PD-1/PD-L1 based immunotherapy to be treated by an HVEM based immunotherapy, comprising receiving a sample from the subject and determining T cell levels in the sample, wherein T cell levels above a predetermined threshold indicates the subject is suitable to be treated by the HVEM based immunotherapy are provided.

Abstract: Agents that bind HVEM, inhibit HVEM-BTLA interaction and activate downstream HVEM signaling are provided. Methods of treating disease with those agents and kits comprising those agents are also provided.