Does PD1/PDL1 Immunotherapy Require Patient Tumor Subgroup Pre-Analysis in the Era of Precision Medicine?

Abstract

Inter-individual variability of the therapeutic response of patients with cancer to anti-PD1 immunotherapy is a determinant for precision medicine. Anti-PD1 monoclonal antibodies (mAb) interact with the PD1 receptor expressed on T cells, hence preventing the recognition of PDL1 ligand on tumor cells and enhancing their cytotoxic effect. The Food & Drug Administration (FDA) as well as the European Medicines Agency (EMA) have approved anti-PD1 mAb for several human cancer therapies, including malignant melanoma, non-small cell lung cancer, renal cancer, urothelial cancer, and Hodgkin's lymphoma. Anti-PD1 mAb can increase overall survival or progression free survival, but in some subgroups of patients they have shown lower or no therapeutic effect. In recent years, expression levels of PDL1 in tumor cells have been recognized as a determinant for predicting the responsiveness to anti-PD1 mAb therapy, however other factors such as age, or somatic mutations might also play a role. Here we propose the pre-evaluation of PD1 receptor expression status as a prerequisite for patient selection for treatment with anti-PD1 mAb-based therapy.