Blocking tumor escape in hematologic malignancies: The anti-PD-1 strategy

• Published in: Blood reviews Vol. 29; no. 1; pp. 25 - 32
• Main Authors: Bryan, Locke J, Gordon, Leo I
• Format: Journal Article
• Language: English
• Published: England Elsevier Ltd 01-01-2015
• Subjects: Animals; Antibodies, Monoclonal - pharmacology; Antibodies, Monoclonal - therapeutic use; Antineoplastic Agents - pharmacology; Antineoplastic Agents - therapeutic use; Clinical Trials as Topic; Follicular lymphoma; Hematologic malignancies; Hematologic Neoplasms - drug therapy; Hematologic Neoplasms - immunology; Hematologic Neoplasms - metabolism; Hematology, Oncology and Palliative Medicine; Hodgkin lymphoma; Humans; Immunotherapy; Molecular Targeted Therapy; Monoclonal antibody; Non-Hodgkin lymphoma (NHL); Plasma cell myeloma (PCM); Programmed Cell Death 1 Receptor - antagonists & inhibitors; Programmed Cell Death 1 Receptor - metabolism; Programmed Death-1 (PD-1); Signal Transduction - drug effects; Treatment Outcome; Tumor Escape - drug effects; Tumor Escape - immunology; Hematologic malignancies; Plasma cell myeloma (PCM); Non-Hodgkin lymphoma (NHL); Follicular lymphoma; Programmed Death-1 (PD-1); Monoclonal antibody; Hodgkin lymphoma
• ISSN: 0268-960X; 1532-1681
• DOI: 10.1016/j.blre.2014.09.004

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.