Challenges and perspectives in the immunotherapy of Hodgkin lymphoma. (November 2017)

• Record Type: Journal Article
• Authors: Michot, Jean-Marie; Lazarovici, Julien; Ghez, David; Danu, Alina; Fermé, Christophe; Bigorgne, Amélie; Ribrag, Vincent; Marabelle, Aurélien; Aspeslagh, Sandrine
• Is Part Of: European journal of cancer. Volume 85(2017)
• Page Start: 67
• Page End: 77
• Publication Date: 2017-11
• Subjects: Anti-programmed death 1 -- Hodgkin lymphoma; Cancer -- Periodicals; Neoplasms -- Periodicals; Cancer -- Périodiques; Cancer; Tumors; Electronic journals; Periodicals; Electronic journals; 616.994
• DOI: 10.1016/j.ejca.2017.08.014
• Languages: English
• ISSNs: 0959-8049

Abstract

Abstract: Hodgkin lymphoma (HL) was one of the first few cancers to be cured first with radiotherapy alone and then with a combination of chemotherapy and radiotherapy. Around 80% of the patients with HL will be cured by first-line therapy. However, the ionising radiation not only produces cytotoxicity but also induces alterations in the microenvironment, and patients often struggle with the long-term consequences of these treatments, such as cardiovascular disorders, lung diseases and secondary malignancies. Hence, it is essential to improve treatments while avoiding delayed side-effects. Immunotherapy is a promising new treatment option for Hodgkin lymphoma, and anti- programmed death-1 (PD1) agents have produced striking results in patients with relapsed or refractory disease. The microenvironment of Hodgkin lymphoma appears to be unique in the field of human disease: the malignant Reed-Sternberg cells only constitute 1% of the cells in the lymphoma, but they are surrounded by an extensive immune infiltrate. Reed-Sternberg cells exhibit 9p24.1/ PD-L1 / PD-L2 copy number alterations and genetic rearrangements associated with programmed cell death ligand 1/ ligand 2 (PD-L1/2) overexpression, together with major histocompatibility complex-I (MHC-I) and major histocompatibility complex-II (MHC-II) downregulation (which may facilitate the tumour's immune evasion). Although HL may be a situation in which defective immune surveillance is restored by anti-PD1 therapy, it challenges our current explanation of how anti-PD1 agents work because MHC-I expression is required for CD8-T-cell-mediated tumour antigen recognition. Here, we review recent attempts to understand the defects in immune recognition in HL and to design an optimal evidence-based treatment for combination with anti-PD1. Highlights: Hodgkin lymphoma (HL) is characterised by an ineffective immune infiltrate which seems addict to the PD1–PD-L1 axis. Anti-PD1 therapy recently yielded high response rates in heavily pre-treated patients with classical HL. New challenges are emerging with immunotherapy – notably about how to convert a partial response into a complete response. Understanding the mechanisms of primary and secondary resistance will be decisive to design future treatment combinations.