title: Programmed death-1 immune checkpoint blockade in the treatment of hematological malignancies.
abstract: The use of tumor-specific monoclonal antibodies (MAbs) has revolutionize the field of cancer immunotherapy. Although treatment of malignant diseases with MAbs is promising, many patients fail to respond or relapse after an initial response. Both solid tumors and hematological malignancies develop mechanisms that enable them to evade the host immune system by usurping immune checkpoint pathways such as PD-1, PD-2, PDL-1, or PDL-2 (programmed cell death protein-1 or 2 and PD-Ligand 1 or 2), which are expressed on activated T cells and on T-regulatory, B cells, natural killers, monocytes, and dendritic cells. One of the most exciting anticancer development in recent years has been the immune checkpoint blockade therapy by using MAbs against immune checkpoint receptor and/or ligands. Anti-PD1 antibodies have been tested in clinical studies that included patients with hematological malignancies and showed remarkable efficacy in Hodgkin lymphoma (HL). In our review, we will focus on the effect of PD-1 activation on hematological malignancies and its role as a therapeutic target. Key messages The programmed death 1 (PD1) immune checkpoint is an important homeostatic mechanism of the immune system that helps in preventing autoimmunity and uncontrolled inflammation in cases of chronic infections. However, PD1 pathway is also operated by a wide variety of malignancies and represents one of the most important mechanisms by which tumor cells escape from the surveillance of the immune system. Blocking of immune checkpoints by the use of monoclonal antibodies opened a new era in the field of cancer immunotherapy. Results from clinical trials are promising, and currently, this approach has been proven effective and safe in patients with solid tumors and hematological malignancies.
authors.affiliation: a Second Department of Internal Medicine , National and Kapodistrian University of Athens , Athens , Greece.
authors.forename: Panagiotis
authors.initials: P
authors.lastname: Tsirigotis
authors.affiliation: b Department of Hematology, Vanderbilt University Medical Center , Nashville , TN , USA.
authors.forename: Bipin N
authors.initials: BN
authors.lastname: Savani
authors.affiliation: c Hematology Division , Chaim Sheba Medical Center , Tel Hashomer , Israel.
authors.forename: Arnon
authors.initials: A
authors.lastname: Nagler
mesh_terms: D000911:Antibodies, Monoclonal / Q000494:pharmacology / Q000627:therapeutic use*; D002986:Clinical Trials as Topic; D019337:Hematologic Neoplasms / Q000378:metabolism / Q000628:therapy*; D006801:Humans; D058990:Molecular Targeted Therapy; D061026:Programmed Cell Death 1 Receptor / Q000037:antagonists & inhibitors*; D015398:Signal Transduction / Q000187:drug effects; D016896:Treatment Outcome
chemical_list: D000911:Antibodies, Monoclonal; C105992:PDCD1 protein, human; D061026:Programmed Cell Death 1 Receptor
keywords: Hematological malignancies; immune checkpoint; leukemia; lymphoma; monoclonal antibodies; programmed death-1; targeted therapy; toxicity