{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,14]],"date-time":"2026-02-14T08:55:52Z","timestamp":1771059352379,"version":"3.50.1"},"reference-count":152,"publisher":"MDPI AG","issue":"4","license":[{"start":{"date-parts":[[2023,2,5]],"date-time":"2023-02-05T00:00:00Z","timestamp":1675555200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Associazione Italiana per la Ricerca sul Cancro Foundation Milan","award":["5 \u00d7 1000 No. 21198"],"award-info":[{"award-number":["5 \u00d7 1000 No. 21198"]}]},{"name":"Associazione Italiana per la Ricerca sul Cancro Foundation Milan","award":["PRIN; 2015ZMRFEA"],"award-info":[{"award-number":["PRIN; 2015ZMRFEA"]}]},{"name":"Associazione Italiana per la Ricerca sul Cancro Foundation Milan","award":["RF-2018-12365790"],"award-info":[{"award-number":["RF-2018-12365790"]}]},{"name":"Progetti di Rilevante Interesse Nazionale","award":["5 \u00d7 1000 No. 21198"],"award-info":[{"award-number":["5 \u00d7 1000 No. 21198"]}]},{"name":"Progetti di Rilevante Interesse Nazionale","award":["PRIN; 2015ZMRFEA"],"award-info":[{"award-number":["PRIN; 2015ZMRFEA"]}]},{"name":"Progetti di Rilevante Interesse Nazionale","award":["RF-2018-12365790"],"award-info":[{"award-number":["RF-2018-12365790"]}]},{"name":"the AGING Project\u2014Department of Excellence\u2014DIMET, Universit\u00e0 del Piemonte Orientale, Novara, Italy","award":["5 \u00d7 1000 No. 21198"],"award-info":[{"award-number":["5 \u00d7 1000 No. 21198"]}]},{"name":"the AGING Project\u2014Department of Excellence\u2014DIMET, Universit\u00e0 del Piemonte Orientale, Novara, Italy","award":["PRIN; 2015ZMRFEA"],"award-info":[{"award-number":["PRIN; 2015ZMRFEA"]}]},{"name":"the AGING Project\u2014Department of Excellence\u2014DIMET, Universit\u00e0 del Piemonte Orientale, Novara, Italy","award":["RF-2018-12365790"],"award-info":[{"award-number":["RF-2018-12365790"]}]},{"name":"Ricerca Finalizzata 2018","award":["5 \u00d7 1000 No. 21198"],"award-info":[{"award-number":["5 \u00d7 1000 No. 21198"]}]},{"name":"Ricerca Finalizzata 2018","award":["PRIN; 2015ZMRFEA"],"award-info":[{"award-number":["PRIN; 2015ZMRFEA"]}]},{"name":"Ricerca Finalizzata 2018","award":["RF-2018-12365790"],"award-info":[{"award-number":["RF-2018-12365790"]}]},{"name":"AIL Novara Onlus","award":["5 \u00d7 1000 No. 21198"],"award-info":[{"award-number":["5 \u00d7 1000 No. 21198"]}]},{"name":"AIL Novara Onlus","award":["PRIN; 2015ZMRFEA"],"award-info":[{"award-number":["PRIN; 2015ZMRFEA"]}]},{"name":"AIL Novara Onlus","award":["RF-2018-12365790"],"award-info":[{"award-number":["RF-2018-12365790"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cancers"],"abstract":"<jats:p>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.<\/jats:p>","DOI":"10.3390\/cancers15041015","type":"journal-article","created":{"date-parts":[[2023,2,6]],"date-time":"2023-02-06T01:35:13Z","timestamp":1675647313000},"page":"1015","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":10,"title":["Immunological Aspects of Richter Syndrome: From Immune Dysfunction to Immunotherapy"],"prefix":"10.3390","volume":"15","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-3969-0112","authenticated-orcid":false,"given":"Abdurraouf Mokhtar","family":"Mahmoud","sequence":"first","affiliation":[{"name":"Division of Hematology, Department of Translational Medicine, Universit\u00e0 del Piemonte Orientale and Azienda Ospedaliero-Universitaria Maggiore della Carit\u00e0, 28100 Novara, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4681-0151","authenticated-orcid":false,"given":"Gianluca","family":"Gaidano","sequence":"additional","affiliation":[{"name":"Division of Hematology, Department of Translational Medicine, Universit\u00e0 del Piemonte Orientale and Azienda Ospedaliero-Universitaria Maggiore della Carit\u00e0, 28100 Novara, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0389-3268","authenticated-orcid":false,"given":"Samir","family":"Mouhssine","sequence":"additional","affiliation":[{"name":"Division of Hematology, Department of Translational Medicine, Universit\u00e0 del Piemonte Orientale and Azienda Ospedaliero-Universitaria Maggiore della Carit\u00e0, 28100 Novara, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2023,2,5]]},"reference":[{"key":"ref_1","unstructured":"Swerdlow, S.H., Campo, E., Harris, N.L., Jaffe, E.S., Pileri, S.A., Stein, H., and Thiele, J. 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