The integration of immunomodulatory receptor signaling is crucial for the activation status of responding T cells, and modulation of these receptors, and their ligands, may be of therapeutic benefit. Indeed, recent breakthroughs in checkpoint inhibitor therapies, and in particular those that target the PDL1/PD1 interaction, have demonstrated success in numerous oncological indications. Understanding the expression of these receptors and their cognate ligands within the complex cellular architecture of solid tumors will be fundamentally important to the design of the next-generation of immunotherapies.
Bulk RNASeq analysis of primary human tumor tissue revealed the expression of numerous co-stimulatory (LIGHT/HVEM, 41BB/41BBL, OX40/OX40L, GITR/GITRL) and co-inhibitory (Lag3, VISTA, PVR/PVRL2/TIGIT, Tim3/Galectin-9) receptors and ligands within the tumor microenvironment. Using multiparametric flow cytometry, we have profiled the expression of these immunomodulatory receptors and their respective ligands on the major cellular components of the tumor microenvironment and correlated it with expression on cellular subsets within matched peripheral blood.