Biomarkers and immunotherapy: where are we?

Here, we reviewed the recent breakthroughs in the understanding of predictive biomarkers for immune checkpoint inhibitors (ICI) treatment.

ICI have revolutionized cancer therapy enabling novel therapeutic indications in multiple tumor types and increasing the probability of survival in patients with metastatic disease. However, in every considered tumor types only a minority of patients exhibits clear and lasting benefice from ICI treatment, and due to their unique mechanism of action treatment with ICI is also associated with acute clinical toxicities called immune related adverse events (irAEs) that can be life threatening. The approval of the first ICI drug has prompted many exploratory strategies for a variety of biomarkers and have shown that several factors might affect the response to ICI treatment, including tumors intrinsic factors, tumor microenvironment and tumor extrinsic or systemic factor. Currently, only three biomarkers programmed death-ligand 1 (PD-L1), tumor microenvironment and microsatellite instability had the US Food and Drug Administration-approbation with some limitations.

The establishment of valid predictive biomarkers of ICI sensitivity has become a priority to guide patient treatment to maximize the chance of benefit and prevent unnecessary toxicity.