Biomarkers in immune checkpoint inhibition therapy for cancer patients: what is the role of lymphocyte subsets and PD1/PD-L1?

Abstract

Abstract Although durable clinical responses are achieved in a significant number of patients given Immune checkpoint inhibitors (ICI), like anti-CTLA-4 and anti-PD-1 inhibitors, some of the cancers have shown little or no response to ICI therapy. Even within the known responsive cancers, there is often a subset of non-responsive patients. Due to the accelerated FDA approval of these immunotherapies, the biomarker development has not been able to keep pace. Appropriate predictive, prognostic and surrogate biomarkers are needed to maximally exploit the benefits from ICI therapy for correct and timely stratification of patients to treatment, for monitoring treatment effect, and for avoiding costs and unwanted toxicities when therapy is likely to be ineffective. As the number of clinical trials exploring the utility of these treatments, both as stand-alone and as combination therapy for several cancers is escalating dramatically, the need for appropriate biomarkers is further amplified. This review discusses the potential biomarkers being investigated in ICI therapies, focusing mainly on immunohistochemical expression of PDL-1 and the immune correlates. Various immune components discussed here include the cells of innate (natural killer or NK cells) and adaptive (CD4+ and CD8+ cells) immunity, regulatory and inhibitory immune cells (regulatory T cells or Tregs and myeloid derived suppressor cells or MDSCs), as well as cytokines. Immune checkpoint molecule, programmed death receptor ligand-1 (PD-L1) and various molecules and pathways influencing its expression are also discussed.

Keywords

• CTLA-4
• PD-L1
• PD-1
• Immune checkpoint inhibitor therapies
• Immunotherapies
• Biomarkers