biostudies-literatureMahmoud AMAssociazione Italiana per la Ricerca sul CancroMinistero dell'Università e della RicercaMinistero della SaluteUniversity of Eastern Piedmont Amadeo AvogadroMinistero dell'Università e della RicercaAssociazione Italiana Contro le Leucemie Linfomi e Mieloma1015https://www.ebi.ac.uk/biostudies/studies/S-EPMC9954516biostudies-literatureUnknown15(4)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 CLLCancersImmunological Aspects of Richter Syndrome: From Immune Dysfunction to Immunotherapy.PMC9954516AGING projectPRIN 2015ZMRFEA20225 x 1000 No. 21198project RF-2018-12365790Mahmoud AMMouhssine SGaidano GfalseImmunological 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. 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 CLL2023-01-01T00:00:00Z2023 Feb2025-04-25T17:03:22.16Z2025-04-25T17:03:22.16ZS-EPMC99545163683136110.3390/cancers15041015