Identification of responders to immune checkpoint therapy: which biomarkers have the highest value?

Abstract

Evasion of immune recognition by the innate and acquired immune system is a major principle of tumour cells and belongs to the hallmarks of cancer. Immune checkpoint inhibitor-based cancer therapies targeting the co-inhibitory receptors CTLA-4 or PD-1 have received enormous scientific and clinical attention during the last few years, because of promising clinical results observed in the treatment of different cancer entities including melanoma and cutaneous squamous cell carcinoma. However, the enthusiasm about the effects of the immune checkpoint inhibitors is muted as only a subfraction of patients shows a stable clinical response. To predefine the patient cohorts that may benefit from immune checkpoint therapy, rigorous biomarker analyses, which predict the response to these novel therapies, need to be performed. In addition, combination of immune checkpoint therapy with classical DNA-damaging chemotherapy or radiotherapy, which positively affects tumour neo-antigen presentation, appears to be a promising approach in optimizing patients' response. In this review, we briefly summarize important biomarkers for patient stratification and discuss the current limitations of these biomarkers in defining responders vs. non-responders to immune checkpoint therapy.