title: The emerging role of immune checkpoint inhibition in malignant lymphoma.
abstract: To evade elimination by the host immune system, tumor cells commonly exploit physiological immune checkpoint pathways, restraining efficient anti-tumor immune cell function. Growing understanding of the complex dialog between tumor cells and their microenvironment contributed to the development of immune checkpoint inhibitors. This innovative strategy has demonstrated paradigm-shifting clinical activity in various malignancies. Antibodies targeting programmed death 1 and cytotoxic T-lymphocyte-associated protein-4 are also being investigated in lymphoid malignancies with varying levels of activity and a favorable toxicity profile. To date, evaluated only in the setting of relapsed or refractory disease, anti-programmed death 1 antibodies such as nivolumab and pembrolizumab show encouraging response rates particularly in classical Hodgkin lymphoma but also in follicular lymphoma and diffuse-large B-cell lymphoma. As the first immune checkpoint inhibitor in lymphoma, nivolumab was approved for the treatment of relapsed or refractory classical Hodgkin lymphoma by the Food and Drug Administration in May 2016. In this review, we assess the role of the pathways involved and potential rationale of checkpoint inhibition in various lymphoid malignancies. In addition to data from current clinical trials, immune-related side effects, potential limitations and future perspectives including promising combinatory approaches with immune checkpoint inhibition are discussed.
authors.affiliation: Department of Internal Medicine, Division of Hematology, University Hospital Center Zagreb, Croatia.
authors.forename: Ida
authors.initials: I
authors.lastname: Hude
authors.affiliation: Department I of Internal Medicine and German Hodgkin Study Group (GHSG), University Hospital of Cologne, Germany.
authors.forename: Stephanie
authors.initials: S
authors.lastname: Sasse
authors.affiliation: Department I of Internal Medicine and German Hodgkin Study Group (GHSG), University Hospital of Cologne, Germany.
authors.forename: Andreas
authors.initials: A
authors.lastname: Engert
authors.affiliation: Department I of Internal Medicine and German Hodgkin Study Group (GHSG), University Hospital of Cologne, Germany paul.broeckelmann@uk-koeln.de.
authors.forename: Paul J
authors.initials: PJ
authors.lastname: Bröckelmann
mesh_terms: D000911:Antibodies, Monoclonal / Q000494:pharmacology / Q000627:therapeutic use; D000970:Antineoplastic Agents / Q000494:pharmacology / Q000627:therapeutic use*; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000627:therapeutic use; D060890:B7-H1 Antigen / Q000037:antagonists & inhibitors / Q000378:metabolism; D014408:Biomarkers, Tumor / Q000037:antagonists & inhibitors*; D060908:CTLA-4 Antigen / Q000037:antagonists & inhibitors / Q000378:metabolism; D003131:Combined Modality Therapy / Q000009:adverse effects / Q000379:methods; D006801:Humans; D056747:Immunomodulation / Q000187:drug effects*; D008223:Lymphoma / Q000175:diagnosis / Q000188:drug therapy* / Q000276:immunology / Q000378:metabolism; D058990:Molecular Targeted Therapy; D061026:Programmed Cell Death 1 Receptor / Q000037:antagonists & inhibitors / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects; D016176:T-Lymphocyte Subsets / Q000187:drug effects / Q000276:immunology / Q000378:metabolism; D016896:Treatment Outcome
chemical_list: D000911:Antibodies, Monoclonal; D000970:Antineoplastic Agents; D060890:B7-H1 Antigen; D014408:Biomarkers, Tumor; D060908:CTLA-4 Antigen; D061026:Programmed Cell Death 1 Receptor