Immunological Aspects of Richter Syndrome: From Immune Dysfunction to Immunotherapy

Richter Syndrome (RS) is defined as the development of an aggressive lymphoma in patients with a previous or simultaneous diagnosis of chronic lymphocytic leukemia (CLL). Two pathological variants of RS are recognized: diffuse large B-cell lymphoma (DLBCL)-type and Hodgkin lymphoma (HL)-type RS. Dif...

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Bibliographic Details
Published in:Cancers 2023-02, Vol.15 (4), p.1015
Main Authors: Mahmoud, Abdurraouf Mokhtar, Gaidano, Gianluca, Mouhssine, Samir
Format: Article
Language:English
Subjects:
Antigens
B-cell lymphoma
B-cell receptor
Bispecific antibodies
Cancer
Care and treatment
CD19 antigen
Chimeric antigen receptors
Chronic lymphocytic leukemia
Clinical trials
Cloning
Cytokines
Drug delivery
Epidemiology
Epstein-Barr virus
Gene amplification
Genetic transformation
Hodgkin's lymphoma
Immune checkpoint inhibitors
Immune system
Immunoglobulins
Immunology
Immunotherapy
Kinases
Leukemia
Lymphatic system
Lymphocytes
Lymphocytes B
Lymphocytes T
Lymphoma
Medical prognosis
Molecular modelling
Monoclonal antibodies
Mutation
Oncology, Experimental
Pathogenesis
Patients
PD-1 protein
PD-L1 protein
Review
Richter's syndrome
Stem cell transplantation
T cell receptors
Tomography
Tumor microenvironment
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Description
Summary:Richter Syndrome (RS) is defined as the development of an aggressive lymphoma in patients with a previous or simultaneous diagnosis of chronic lymphocytic leukemia (CLL). Two pathological variants of RS are recognized: diffuse large B-cell lymphoma (DLBCL)-type and Hodgkin lymphoma (HL)-type RS. Different molecular mechanisms may explain the pathogenesis of DLBCL-type RS, including genetic lesions, modifications of immune regulators, and B cell receptor (BCR) pathway hyperactivation. Limited data are available for HL-type RS, and its development has been reported to be similar to de novo HL. In this review, we focus on the immune-related pathogenesis and immune system dysfunction of RS, which are linked to BCR over-reactivity, altered function of the immune system due to the underlying CLL, and specific features of the RS tumor microenvironment. The standard of care of this disease consists in chemoimmunotherapy, eventually followed by stem cell transplantation, but limited possibilities are offered to chemo-resistant patients, who represent the majority of RS cases. In order to address this unmet clinical need, several immunotherapeutic approaches have been developed, namely T cell engagement obtained with bispecific antibodies, PD-1/PD-L1 immune checkpoint blockade by the use of monoclonal antibodies, selective drug delivery with antibody-drug conjugates, and targeting malignant cells with anti-CD19 chimeric antigen receptor-T cells.
ISSN:2072-6694
2072-6694
DOI:10.3390/cancers15041015