Krebswissenschaft und -therapie

Circulating Tumor Cells (CTCs) as Biomarker for PD-1/PD-L1 Blockade Immunotherapy

Abstract

Chunyan YUE and Zhiyuan HU

The PD-1/PD-L1 (programmed death-1, programmed death-1 ligand-1) checkpoint is involved in dampening autoimmunity of peripheral tissues to help control local inflammatory responses. It is reported that this pathway activation results in peripheral immunologic tolerance in T cells [1]. As an identified ligand of PD-1, PD-L1 expressed in tumor cells facilitates tumor escape by inducing a net immunosuppressive effect after binding to PD-1 present on the surface of activated T cells and B cells [2]. The enhanced understanding of the complex interplay between the tumor and the immune system has promoted the development of anti-PD therapy for the treatment of human cancers. Antibodies blocking PD-1/PD-L1 have demonstrated durable responses in a number of different advanced malignancies [3,4]. However, while increasing a baseline T-cell-specific immune response, immune checkpoint inhibitors might result in autoimmune-like/ inflammatory side-effects, which cause collateral damage to normal organ systems and tissues, such as skin, lung and liver [5]. Therefore, detection of potential biomarkers that may predict benefit is pivotal in order to optimize clinical efficacy and safety of checkpoint blockade immunotherapy.