Tokine production, and killing of target tumor cells. The higher affinity receptor for TIGIT is PVR, as well as the counter agonist receptor is CD226, all of which are members in the PVR-nectin family members. TIGIT is elevated inside the tumor microenvironment in a lot of human tumors and coordinately expressed with other checkpoint immune receptors which include PD-1. On the other hand, the spatial and coordinate expression of those receptors and ligands needed for these functions, along with the celltypes involved in anti-tumor immunity, remains unknown. Solutions TIGIT, CD226 and PD-L1 blockade are going to be assessed in preclinical syngeneic tumor model CT26 and MC38. To figure out which immune cells are important for permitting tumor progression early and late in disease mice with cell-specific gene ablation for these family members were challenged with tumors. Tumor growth was determined and tumor sections labeled and probed by fluorescence microscopy to assess TIGIT, CD226 and PVR cellular expression. Outcomes In mouse models of each cancer, antibody co-blockade of TIGIT and PD-L1 enhanced CD8+ T cell effector function, resulting in significant tumor clearance. TIGIT is expressed on CD8+ T cell, Treg and NK cells. Certain ablation of TIGIT on CD8+ T cells resulted in tumor clearance, and was dependent on PVR in the host tissue. Immunofluorescence studies are going to be presented. Conclusions Therapeutic blockade of TIGIT may well result in improved eradication of malignancies when used in conjunction with other anti-cancer therapies such as these that modulate anti-tumor immune responses, and is at present becoming tested in phase I clinical trials. Models indicate that inhibition of TIGIT with a blocking mAb might release CD226 to activate tumor-specific T cells. An additional mechanism could involve regulation of T cell suppression by TIGIT on regulatory T cells. A much better understanding from the coordinate interaction Bax Inhibitor Synonyms amongst these receptors and ligands in tumors are going to be informative for the appropriate application of checkpoint-therapy combinations. P210 CC-122 in mixture with immune checkpoint blockade synergistically activates T cells and enhances immune mediated killing of HCC cells Patrick Hagner1, Hsiling Chiu1, Michelle Waldman1, Anke Klippel1, Anjan Thakurta1, Michael Pourdehnad2, Anita Gandhi1 1 Celgene Corporation, Summit, NJ, USA; 2Celgene Corporation, San Francisco, CA, USA Correspondence: Patrick Hagner ([email protected]) Journal for ImmunoTherapy of Cancer 2016, four(Suppl 1):PP208 Monoclonal antibodies targeting phosphatidylserine boost combinational activity from the immune checkpoint targeting agents LAG3 and PD-1 in murine breast tumors Michael Gray, Jian Gong, Jeff Hutchins, Bruce Freimark Peregrine Pharmaceuticals, Tustin, CA, USA Correspondence: Michael Gray ([email protected]) Journal for ImmunoTherapy of Cancer 2016, 4(Suppl 1):P208 Background Our prior work demonstrated that the addition of phosphatidylserine (PS) targeting antibodies to anti-programmed death ligand 1 (PD-1) therapy in murine triple damaging breast cancers (TNBC) drastically enhanced immune technique activation and tumor growth inhibition. In these studies, NanoString immune profile analysis showed that intratumoral levels of lymphocyte activation gene three (LAG3) mRNA increased in response to PS and PD-1 treatments. This suggests LAG3 could act to attenuate T cell activation in TNBC throughout I/O therapeutic regimens; however, it’s unknown if PD-1 and LAG3 function cooperatively in regulating T cell IDO Inhibitor list anergy, and wh.