ISSN 2997-1036
International Journal of Hematology | Vol. 7, No. 11, November 2016 | pp. 81–88
DOI: 10.46882/2016/IJH/000083
Review Article
Title: Evolving mechanisms of immune escape and therapeutic checkpoint blockade targets in classical Hodgkin lymphoma
Names of Authors: M. A. Bello¹, O. R. Eze²
Authors’ Affiliations: ¹Department of Haematology, Aminu Kano Teaching Hospital, Kano, Nigeria; ²Department of Pathology, University of Benin, Benin City, Nigeria
Abstract: Classical Hodgkin lymphoma is characterized by a unique tumor microenvironment where neoplastic Hodgkin and Reed-Sternberg cells are outnumbered by an abundant background of non-neoplastic inflammatory cells. This review examines the complex molecular structural mechanisms of microenvironmental immune escape, focusing on the genetic amplification of the 9p24.1 locus, which drives over-expression of programmed death ligands 1 and 2 (PD-L1 and PD-L2) on Reed-Sternberg cells. This ligand upregulation leads to direct binding with PD-1 receptors on tumor-infiltrating T lymphocytes, downregulating cytotoxic immune responses and inducing immune exhaustion. Evolving therapeutic models focus on restoring immune recognition via monoclonal antibodies targeting the PD-1 axis, such as nivolumab and pembrolizumab. Clinical trials evaluating checkpoint inhibitors in relapsed or refractory settings demonstrate remarkable efficacy, achieving objective response rates of 65% to 70% even after autologous stem cell transplantation failures. However, immune-related adverse events, including pneumonitis and thyroiditis, require proactive management algorithms. This review outlines structural biomarkers, tissue PD-L1 expression metrics, and clinical combination pathways designed to optimize checkpoint therapy and maximize long-term survival in refractory Hodgkin lymphoma cohorts.
Keywords: Classical Hodgkin lymphoma, Reed-Sternberg cells, immune escape, PD-1 checkpoint, microenvironment
Manuscript Timeline: Received: August 20, 2016; Revised: September 25, 2016; Accepted: October 14, 2016; Published: November 19, 2016