By Radha Krishnan, M.D., Chief Pathologist and Senior Medical Director; Patrice Hugo, Ph.D., Chief Scientific Officer
Advances in precision medicine have led to a paradigm shift for oncology research, from targeted therapies that rely largely on tyrosine kinase inhibitors (TKIs) to personalized therapy that can deliver demonstrable improvement in patient response along with considerably lower side effects. At the center of this shift is immunotherapy, in which researchers are developing drugs that harness the patient’s immune system to fight the cancer on its own. This research area has seen the introduction of new drugs, such as immune checkpoint inhibitors that target various pathways like Cytotoxic T-Lymphocyte Antigen 4 (CTLA-4), Programmed Cell Death Protein 1 (PD-1) or Programmed Death-Ligand 1 (PD-L1) Such immuno-therapeutics are now representing a significant proportion of all oncology drugs recently approved.
As we look to the future of immunotherapy, PD-L1 testing will become even more important, as not all solid tumors express PD-L1 and hence are appropriate for PD-1/PD-L1 immune checkpoint inhibitor therapy. The PD-L1 immunohistochemistry (IHC) assay is the standard tool to assess PD-L1 increased expression in tumor cells as well as in the tumor microenvironment. The PD-L1 IHC is currently developed as a companion diagnostic assay and predictive biomarker to identify patients, which are more likely to benefit (i.e. responders) to PD-1/PD-L1 drugs.
Continued investigations into tumor biomarkers, tumor micro- environment and pharmacodynamics expect to provide insights into the mechanism of action of PD-L1, and guide future development of synergistic combination therapy with combination of cancer vaccine and immune checkpoint inhibitors, and/or chemotherapy.