Development and applications of computer image analysis algorithms for scoring of PD-L1 immunohistochemistry

Immune checkpoint inhibitors targeting programmed cell death 1 (PD-1) and programmed cell death ligand 1 (PD-L1) have rapidly become integral to standard-of-care therapy for non-small cell lung cancer and other cancers. Immunohistochemical (IHC) staining of PD-L1 is currently the accepted and approved diagnostic assay for selecting patients for PD-L1/PD-1 axis therapies in certain indications. However, the inherent biological complexity of PD-L1 and the availability of several PD-L1 assays - each with different detection systems, platforms, scoring algorithms and cut-offs - have created challenges to ensure reliable and reproducible results based on subjective visual assessment by pathologists. The increasing adoption of computer technologies into the daily workflow of pathology provides an opportunity to leverage these tools towards improving the clinical value of PD-L1 IHC assays. This review describes several image analysis software programs of computer-aided PD-L1 scoring in the hope of driving further discussion and technological advancement in digital pathology and artificial intelligence approaches, particularly as precision medicine evolves to encompass accurate simultaneous assessment of multiple features of cancer cells and their interactions with the tumor microenvironment.