title: Where Do Programmed Death-1 Inhibitors Fit in the Management of Malignant Lymphoma?
abstract: Tumor-specific cytotoxic T cells have the capacity to target and eradicate malignant B cells in patients with Hodgkin and non-Hodgkin lymphoma; however, multiple mechanisms, including regulatory T cells, immunosuppressive ligands, and immune exhaustion, suppress an effective antitumor immune response. One mechanism that is used by malignant cells to inhibit the immune response is overexpression of programmed death ligand 1 or 2 (PD-L1 or PD-L2) on the cancer cell surface. These ligands interact with the programmed death-1 (PD-1) receptor expressed on intratumoral T cells and provide an inhibitory signal, thereby suppressing the antitumor immune response. Monoclonal antibodies that block PD-1 signaling prevent T-cell inhibition and promote a T-cell-mediated antilymphoma response. Blocking antibodies that are directed against PD-1 or PD-L1 are currently being tested in patients with lymphoma and have shown remarkable efficacy, particularly in patients with relapsed Hodgkin lymphoma. On the basis of the promising activity of this approach, PD-1 inhibitors are being used as single-agent therapy in patients with relapsed Hodgkin lymphoma, and these inhibitors are also being tested in combination with standard chemotherapy or targeted agents in ongoing clinical trials.
authors: Mayo Clinic, Rochester, MN ansell.stephen@mayo.edu.
authors: Stephen M
authors: SM
authors: Ansell
mesh_terms: D000911:Antibodies, Monoclonal / Q000494:pharmacology / Q000627:therapeutic use*; D000970:Antineoplastic Agents / Q000494:pharmacology / Q000627:therapeutic use*; D060890:B7-H1 Antigen / Q000378:metabolism; D002986:Clinical Trials as Topic; D019468:Disease Management; D006801:Humans; D008223:Lymphoma / Q000175:diagnosis / Q000188:drug therapy* / Q000209:etiology / Q000378:metabolism; D061026:Programmed Cell Death 1 Receptor / Q000037:antagonists & inhibitors* / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects; D016896:Treatment Outcome
chemical_list: D000911:Antibodies, Monoclonal; D000970:Antineoplastic Agents; D060890:B7-H1 Antigen; D061026:Programmed Cell Death 1 Receptor