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
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
Externí odkaz: