The immune system plays a fundamental role in tumor biology, and the ability to avoid immune destruction has been recognized as an emerging hallmark of cancer. Many tumors elicit an immune response, especially those demonstrating a high mutational burden. It is now clear that evasion of an immune response is made possible by a variety of different mechanisms, such as suppression of the antigen-presenting machinery, expression of various immune checkpoint inhibitors by tumor cells, and tumor-infiltrating immune cells.
Therapies directed against programmed cell death protein 1 (PD-1) and/or programmed death-ligand 1 (PD-L1) have recently been approved for a variety of different indications. These therapies have demonstrated durable responses in a subset of patients. PD-L1 (CD274 gene product) is expressed in a large variety of tumor types, on tumor cells as well as immune cells in the tumor microenvironment. Assessing the expression of PD-L1 by immunohistochemistry (IHC) can aid in the selection of patients who may benefit most from anti-PD-1/PD-L1 therapies; however, 10-20% of tumors lacking expression of PD-L1 may still derive benefit. There are several PD-L1 IHC kits which have received US Food and Drug Administration (FDA) approval that use different clones, detection system, and cut-offs complicating the execution and interpretation of results. Potential new biomarkers are being assessed in ongoing clinical trials.
- Review the adaptive immune response
- Describe the PD-L1 pathway
- Highlight the differences and similarities between the FDA approved PD-L1 assays
- Review the relationship between PD-L1 expression and emerging biomarkers
Kenneth J. Bloom, MD, FCAP (Presenter)
Jordan S. Laser, MD, FCAP (Host)