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Update on checkpoint blockade therapy for lymphoma
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 tha...
Autores principales: | , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
BioMed Central
2015
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4509696/ https://www.ncbi.nlm.nih.gov/pubmed/26199729 http://dx.doi.org/10.1186/s40425-015-0079-8 |
Sumario: | 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. |
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