Spatiotemporal Changes in Checkpoint Molecule Expression

Immune checkpoint inhibitors (ICIs), particularly PD-1/PD-L1 blockade, have led to therapeutic breakthrough in patients with advanced malignancy, covering the lung, breast, gastrointestinal, head and neck, urinary system, lymphoma, and solid tumor harboring MSI/dMMR. In certain cancer types, the expression level of immune checkpoint molecule will be required if the immune-based approaches are considered, especially the PD-L1 expression. However, in other types, survival benefit has been proven regardless of PD-L1 expression. It raises a question of how to select patients for immune therapy and whether the expression of immune checkpoint molecules will be optimal biomarkers. Before answering this question, a comprehensive map for the expression of immune checkpoint molecules is needed. In this chapter, we describe our current knowledge on the spatiotemporal changes in the expression of checkpoint molecules. We discuss the different frequencies of expression depending on tumor types and stages, the different patterns between primary and metastatic tumors, as well as the change of expression before and after treatment. The expression of PD-L1 has been most studied, but the threshold that separate “positive” and “negative” PD-L1 expressions and the consistency of testing platform remain under debate. Better understanding on the tumor microenvironment and expression of checkpoint molecules will help to identify patients who will benefit from checkpoint blockade therapy.