Abstract
In recent years, the role of cancer immunotherapy has become increasingly important compared to traditional cancer treatments, including surgery, chemotherapy and radiotherapy. Of note, the clinical successes of immune checkpoint blockade, such as PD-1 and CTLA-4, represent a landmark event in cancer immunotherapy development. Therefore, further exploration of how immune checkpoints are regulated in the tumor microenvironment will provide key insights into checkpoint blockade therapy. In this review, we discuss in details about the regulation of immune checkpoints mediated by immune cells, oncolytic viruses, epigenetics, and gut microbiota and mutual regulation by co-expressed checkpoints. Finally, predictions are made for future personalized cancer immunotherapy based on different checkpoint modulations.
Highlights
Cancer, a disease associated with cell growth caused by genetic mutations, is known to activate proto-oncogenes
Cancer immunotherapies targeting immune checkpoints have recently revolutionized cancer treatments. These treatments function through the blockade of immunosuppressive checkpoints, such as PD-1, cytotoxic T-lymphocyte protein-4 (CTLA-4), and TIGIT, and the activation of immunostimulatory checkpoints, such as CD226 and CD28, in effector T-cells and myeloid cells [2,3,4,5,6]
We focused on different aspects of the regulation of immune checkpoints in the tumor microenvironment (TME), including regulation mediated by immune cells in the TME, oncolytic viruses, the function of epigenetic modulators, the role of intestinal flora and mutual regulation by various immune checkpoints
Summary
A disease associated with cell growth caused by genetic mutations, is known to activate proto-oncogenes. Cancer immunotherapies targeting immune checkpoints have recently revolutionized cancer treatments These treatments function through the blockade of immunosuppressive checkpoints, such as PD-1, CTLA-4, and TIGIT, and the activation of immunostimulatory checkpoints, such as CD226 and CD28, in effector T-cells and myeloid cells [2,3,4,5,6]. Immunosuppressive checkpoints can inhibit immune responses mainly via interfernece with CD3/CD28-dependent signaling, competitive interruption of B7 family binding to co-stimulatory molecules or via transmission of supressive signals into tumor cells or T cells. Two of these checkpoints, namely, programmed cell death protein-1 (PD-1) and cytotoxic T-lymphocyte protein-4 (CTLA-4), have become the focus of this attention. We expect to carry out more accurate and effective personalized cancer immunotherapy, after considering the different levels of checkpoint expression among patients based on the regulation mediated by different factors
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Free) 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
