Abstract
Targeting the immune checkpoint receptors cytotoxic T lymphocyte antigen 4 (CTLA-4), programmed cell death protein 1 (PD-1), or programmed cell death 1 ligand 1 (PD-L1) represents a very attractive treatment modality for tumor patients. The administration of antibodies against these receptors can promote efficient antitumor effects and can induce objective clinical responses in about 20–40% patients with various tumor types, accompanied by improved survival. Based on their therapeutic efficiency, several antibodies have been approved for the treatment of tumor patients. However, many patients do not respond to checkpoint inhibitor therapy. Therefore, the identification of biomarkers is required to guide patient selection for this treatment modality. Here, we summarize recent studies investigating the PD-L1 expression or mutational load of tumor tissues as well as the frequency and phenotype of immune cells in tumor patients prior to and during CTLA-4 or PD-1/PD-L1 inhibitor treatment.
Highlights
In recent years, immunotherapy of tumors has gained much momentum by the development of novel promising treatment modalities that have been considered as a scientific breakthrough [1]
One of these encouraging strategies is based on the inhibition of immune checkpoint molecules, resulting in improved antitumor responses mediated by CD4+ and CD8+ T lymphocytes [2,3]
It has been demonstrated that activation of the protein phosphatases SHP2 and PP2A may play an essential role in counteracting kinase signals that are induced by T cell receptor (TCR) and CD28 [17]
Summary
Immunotherapy of tumors has gained much momentum by the development of novel promising treatment modalities that have been considered as a scientific breakthrough [1] One of these encouraging strategies is based on the inhibition of immune checkpoint molecules, resulting in improved antitumor responses mediated by CD4+ and CD8+ T lymphocytes [2,3]. Agonist antibodies for costimulatory pathways or antagonist antibodies for inhibitory pathways are in current clinical testing [2,3,8] Both approaches aim at the amplification and activation of antigen-specific T cell responses, enhancing the endogenous antitumor activity. Immune monitoring technologies help by providing novel insights into the mechanisms underlying checkpoint inhibitor therapy and by identifying potential modes of resistance to treatment. We review recent studies exploring the PD-L1 expression or mutational load of tumor tissues as well as the frequency and phenotype of tumor-infiltrating or blood-circulating immune cells in tumor patients prior to and during checkpoint inhibitor therapy
Sign-in/Register to view highlights & summary 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 callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
