title: Update on checkpoint blockade therapy for lymphoma.
abstract: Although cancer cells express antigens recognizable to the immune system, tumors employ a number of diverse mechanisms aimed at subverting the host anti-tumor immune response. Tumor immune evasion pathways have been most thoroughly studied in solid tumors. However, emerging data has demonstrated that malignancies of hematopoietic origin are also able to co-opt their local environment in order to escape immune attack. Activated T cells upregulate negative costimulatory receptors, such as programmed death-1 (PD-1) and cytotoxic lymphocyte antigen-4 (CTLA-4). Engagement of PD-1 or CTLA-4 with ligands expressed on tumor cells or professional antigen presenting cells results in down-regulation of effector T cell function and represents a potent mechanism of immune evasion across a number of human cancers. Antibodies which block PD-1 / PD-L1 interactions have demonstrated remarkable activity in a number of solid tumor subtypes. Interestingly, recent data have demonstrated that in select subtypes of Hodgkin (HL) and non-Hodgkin lymphoma (NHL), the PD-1 ligands are over-expressed due to a genetic amplification of the loci encoding them. Other mechanisms of PD-L1 over-expression in lymphoma have also been elucidated. Reports from early-phase clinical trials of PD-1 blockade have demonstrated remarkable effectiveness in HL, and also appear active against some NHLs. We review the mechanisms of PD-L1 expression in lymphoma and also the early results of anti-PD-1 therapy in this disease.
authors.affiliation: Department of Medicine, University of Chicago, 5841 S. Maryland Ave., MC2115, Chicago, IL 60637 USA ; Committee on Immunology, University of Chicago, Chicago, IL USA.
authors.forename: Justin
authors.initials: J
authors.lastname: Kline
authors.affiliation: Department of Medicine, University of Chicago, 5841 S. Maryland Ave., MC2115, Chicago, IL 60637 USA.
authors.forename: Michael R
authors.initials: MR
authors.lastname: Bishop