Affiliation:
1. Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA
Abstract
Abstract
Classical Hodgkin lymphoma (cHL) is an unusual B-cell–derived malignancy in which rare malignant Hodgkin and Reed-Sternberg (HRS) cells are surrounded by an extensive but ineffective inflammatory/immune cell infiltrate. This striking feature suggests that malignant HRS cells escape immunosurveillance and interact with immune cells in the cancer microenvironment for survival and growth. We previously found that cHLs have a genetic basis for immune evasion: near-uniform copy number alterations of chromosome 9p24.1 and the associated PD-1 ligand loci, CD274/PD-L1 and PDCD1LG2/PD-L2, and copy number–dependent increased expression of these ligands. HRS cells expressing PD-1 ligands are thought to engage PD-1 receptor–positive immune effectors in the tumor microenvironment and induce PD-1 signaling and associated immune evasion. The genetic bases of enhanced PD-1 signaling in cHL make these tumors uniquely sensitive to PD-1 blockade.
Publisher
American Society of Hematology
Subject
Cell Biology,Hematology,Immunology,Biochemistry
Cited by
46 articles.
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