title: Blocking tumor escape in hematologic malignancies: the anti-PD-1 strategy.
abstract: Immunotherapy remains an important tool for treatment of hematologic malignancies. The Programmed Death-1 (PD-1) immune checkpoint pathway has emerged as a mechanism of tumor evasion from the anti-tumor immune response. The recent development of anti-PD-1 monoclonal antibodies has offered a targeted approach to cancer therapy. Several agents are in various stages of development and have shown clinical responses across a broad spectrum of both solid and hematologic malignancies. The use of anti-PD-1 therapy in hematologic malignancies is limited but has demonstrated clinical responses in relapsed/refractory disease following multiple lines of therapy. PD-1 blockade may reduce relapse rates for patients who fail to obtain a complete remission prior to autologous hematopoietic cell transplant. The role of the PD-1 pathway for tumor escape is reviewed. We explore the use of anti-PD-1 therapy in hematologic malignancies. The proposed mechanism of PD-1 blockade as a modulator of the innate and acquired immune response is considered. Finally, the challenges of anti-PD-1 therapy and the future direction of investigation in this area are reviewed.
authors.affiliation: Division of Hematology/Oncology, Feinberg School of Medicine, Northwestern University, 676 N St Clair, Suite 850, Chicago, IL 60611, USA. Electronic address: locke.bryan@northwestern.edu.
authors.forename: Locke J
authors.initials: LJ
authors.lastname: Bryan
authors.affiliation: Division of Hematology/Oncology, Robert H. Lurie Comprehensive Cancer Center, 676 N St Clair, Suite 850, Chicago, IL 60611, USA. Electronic address: l-gordon@northwestern.edu.
authors.forename: Leo I
authors.initials: LI
authors.lastname: Gordon
mesh_terms: D000818:Animals; D000911:Antibodies, Monoclonal / Q000494:pharmacology / Q000627:therapeutic use*; D000970:Antineoplastic Agents / Q000494:pharmacology / Q000627:therapeutic use*; D002986:Clinical Trials as Topic; D019337:Hematologic Neoplasms / Q000188:drug therapy* / Q000276:immunology / Q000378:metabolism; D006801:Humans; D007167:Immunotherapy; D058990:Molecular Targeted Therapy; D061026:Programmed Cell Death 1 Receptor / Q000037:antagonists & inhibitors* / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects; D016896:Treatment Outcome; D019139:Tumor Escape / Q000187:drug effects* / Q000276:immunology
chemical_list: D000911:Antibodies, Monoclonal; D000970:Antineoplastic Agents; D061026:Programmed Cell Death 1 Receptor
keywords: Follicular lymphoma; Hematologic malignancies; Hodgkin lymphoma; Monoclonal antibody; Non-Hodgkin lymphoma (NHL); Plasma cell myeloma (PCM); Programmed Death-1 (PD-1)