title: Beginning of a novel frontier: T-cell-directed immune manipulation in lymphomas.
abstract: Checkpoint inhibitors with monoclonal antibodies targeting the CTLA-4 or PD-1 axis have revolutionized treatment in some solid tumors, especially melanoma and lung. The role of the CTLA-4 and PD-1 pathways and their inhibition in lymphoma may be different compared to solid tumors. In heavily pretreated Hodgkin lymphoma, PD-1-directed treatment has led to high remission rates. Several studies are now conducted also including diffuse large B-cell and follicular lymphoma. Besides antibody-based immunotherapy, treatment with chimeric antigen receptor (CAR) T-cells has also come back to the focus of recent studies. Clinical evidence of CAR T-cell treatment in B-cell malignancies is limited to small series, because of the dedicated resources needed. However, impressive response rates have been observed, but toxicities associated with cytokine release can be very severe and fatal. We herein review the background, early clinical evidence, and future perspectives of T-cell-directed immune manipulation for lymphomas including checkpoint inhibitors and CAR T-cell therapies.
authors.affiliation: a Department of Medicine , Royal Marsden Hospital , Sutton , UK.
authors.forename: Benjamin
authors.initials: B
authors.lastname: Kasenda
authors.affiliation: a Department of Medicine , Royal Marsden Hospital , Sutton , UK.
authors.forename: Andrea
authors.initials: A
authors.lastname: Kühnl
authors.affiliation: a Department of Medicine , Royal Marsden Hospital , Sutton , UK.
authors.forename: Ian
authors.initials: I
authors.lastname: Chau
mesh_terms: D000818:Animals; D000911:Antibodies, Monoclonal / Q000494:pharmacology / Q000627:therapeutic use; D000951:Antigens, Neoplasm / Q000276:immunology / Q000378:metabolism; D000970:Antineoplastic Agents / Q000494:pharmacology / Q000627:therapeutic use; D015415:Biomarkers; D060908:CTLA-4 Antigen / Q000037:antagonists & inhibitors; D064987:Cell- and Tissue-Based Therapy; D006801:Humans; D056747:Immunomodulation / Q000187:drug effects; D016219:Immunotherapy, Adoptive / Q000009:adverse effects / Q000379:methods; D008223:Lymphoma / Q000175:diagnosis / Q000235:genetics / Q000276:immunology* / Q000378:metabolism / Q000628:therapy*; D061026:Programmed Cell Death 1 Receptor / Q000037:antagonists & inhibitors; D011485:Protein Binding; D011948:Receptors, Antigen, T-Cell / Q000235:genetics / Q000378:metabolism; D011993:Recombinant Fusion Proteins / Q000235:genetics / Q000378:metabolism; D016176:T-Lymphocyte Subsets / Q000187:drug effects / Q000276:immunology* / Q000378:metabolism; D016896:Treatment Outcome
chemical_list: D000911:Antibodies, Monoclonal; D000951:Antigens, Neoplasm; D000970:Antineoplastic Agents; D015415:Biomarkers; D060908:CTLA-4 Antigen; D061026:Programmed Cell Death 1 Receptor; D011948:Receptors, Antigen, T-Cell; D011993:Recombinant Fusion Proteins
keywords: CAR; Lymphoma; T-cells; anti-PD-1 treatment; chimeric antibody receptor; immunotherapy; ipilimumab; nivolumab; pembrolizumab; pidilizumab; review