Signaling Pathways and Immune Checkpoint Regulation in Cancer

Dear colleagues,

Intensive research over the last decades has uncovered the dynamic interactions between cancer cells and host immune cells, namely T-lymphocytes, NK cells, dendritic cells and histiocytes. The immune checkpoint plays a crucial role in the immune response against tumor cells, and therefore, better understanding of the underlying mechanisms led to the development of novel immunotherapeutic approaches in cancer. The basic concept of immunotherapy is that the target molecule is on the immune cell and not on the tumor cell, and therefore the same strategy would work on many different cancer cell types with different phenotype and genetic backgrounds. Immune checkpoint therapy initially focused on CTLA-4 with promising results. More recently, the PD-1 (programmed death-1) and its ligand (PD-L1) have been targeted with anti-PD-1 and anti-PD-L1 antibodies, which are currently being tested in clinical trials in a variety of cancers with clinical success. In certain tumor types, immunotherapy efficiency has been associated with PD-L1 protein levels. PD-L1 expression can be regulated at the genetic (e.g. PD-L1 gene amplification), transcriptional and post-translational level, however, the exact mechanisms may be cell type-specific and they are still under investigation. Transcription factors, known to regulate PD-L1 gene expression, commonly operate as targets of known oncogenic signaling pathways, thus providing the biologic rationale for combination treatment strategies such as immunotherapy with targeted therapy.

This Special Issue focuses on the mechanisms of immune checkpoint regulation by oncogenic signaling pathways that may represent novel therapeutic targets, as well as the role of the tumor microenvironment. In addition, immunotherapy-related studies including PD-1/PD-L1 antibodies and CART-T cell therapy are most welcome for publication consideration in this issue.

Prof. Dr. Georgios Rassidakis
Guest Editor

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