Challenges and perspectives in the immunotherapy of Hodgkin lymphoma
Autor: | Jean-Marie Michot, Christophe Fermé, David Ghez, Sandrine Aspeslagh, Julien Lazarovici, Amélie Bigorgne, Alina Danu, Vincent Ribrag, Aurélien Marabelle |
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Přispěvatelé: | Medical Oncology |
Rok vydání: | 2017 |
Předmět: |
0301 basic medicine
Cancer Research medicine.medical_treatment Programmed Cell Death 1 Receptor Tumor Escape/drug effects 0302 clinical medicine Signal Transduction/drug effects hemic and lymphatic diseases Tumor Microenvironment Molecular Targeted Therapy Reed-Sternberg Cells Cytotoxicity Child Aged 80 and over biology Reed-Sternberg Cells/drug effects Programmed Cell Death 1 Receptor/antagonists & inhibitors Middle Aged Hodgkin Disease Treatment Outcome Oncology 030220 oncology & carcinogenesis Immunotherapy Biomarkers Tumor/antagonists & inhibitors Antibodies/adverse effects Signal Transduction Adult Adolescent Antineoplastic Agents Major histocompatibility complex Antibodies 03 medical and health sciences Young Adult Immune system medicine Biomarkers Tumor Humans Aged Chemotherapy Tumor microenvironment business.industry Antineoplastic Agents/adverse effects medicine.disease Hodgkin Disease/genetics Lymphoma Radiation therapy Immunotherapy/adverse effects 030104 developmental biology Immunology biology.protein Tumor Escape business |
Zdroj: | European journal of cancer (Oxford, England : 1990). 85 |
ISSN: | 1879-0852 |
Popis: | 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. |
Databáze: | OpenAIRE |
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