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Cancers
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Recent Advances in Hodgkin’s Lymphoma
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Recent Advances in Hodgkin’s Lymphoma

A special issue of Cancers (ISSN 2072-6694). This special issue belongs to the section "Molecular Cancer Biology".

Deadline for manuscript submissions: closed (31 December 2020) | Viewed by 14108

Special Issue Editor

Prof. Dr. Massimo Mascolo

E-Mail Website
Guest Editor
Pathology Unit, Department of Advanced Biomedical Sciences, University Federico II of Naples, 80131 Naples, Italy
Interests: pathology; surgical pathology; oncologic pathology; molecular pathology; dermatopathology; hematopathology; head and neck pathology; endocrine pathology; nodal and extranodal lymphoma
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

Hodgkin’s lymphoma (HL) is a hematopoietic neoplasm arising from the B-cells of the germinal center or post-germinal center. It accounts for 10% of all lymphomas and mainly occurs in the first four decades, representing the most common cancer diagnosed in the age range 15–19. The therapeutic pillars for HL are chemotherapy and radiotherapy, alone or in combination, and, more recently, autologous stem-cell transplant and immunotherapy. While most patients respond excellently to first-line therapy, a subset of patients (approximately 15%) either does not respond or relapses, presenting extremely poor clinical outcomes. The need for effective new therapies is evident for these patients. Although several therapeutic strategies have been developed based on targeting signalling pathways, few specific prospective studies are still being performed. Pathways associated with development and tissue homeostasis, such as NF-κB, Notch, JAK/STAT, as well as the tumour microenvironment, are involved in the pathogenesis of this disease. Recently, the pathogenic role of non-malignant lymphoid subpopulations within the tumour cells is emerging. Therefore, a better understanding of its pathogenesis is of high relevance to develop future targeted therapies for this disease. This Special Issue aims to provide an updated overview of recent advances in the biology and molecular oncology of Hodgkin’s lymphoma and their repercussions on diagnosis, therapy, and outcome, highlighting the prospects for improving patient management.

Prof. Dr. Massimo Mascolo
Guest Editor

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All submissions that pass pre-check are peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. Cancers is an international peer-reviewed open access semimonthly journal published by MDPI.

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Published Papers (4 papers)

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Research

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14 pages, 1070 KiB  
Article
Rituximab-Containing Risk-Adapted Treatment Strategy in Nodular Lymphocyte Predominant Hodgkin Lymphoma: 7-Years Follow-Up
by Novella Pugliese, Marco Picardi, Roberta Della Pepa, Claudia Giordano, Francesco Muriano, Aldo Leone, Giuseppe Delle Cave, Alessandro D’Ambrosio, Violetta Marafioti, Maria Gabriella Rascato, Daniela Russo, Massimo Mascolo and Fabrizio Pane
Cancers 2021, 13(8), 1760; https://doi.org/10.3390/cancers13081760 - 7 Apr 2021
Cited by 8 | Viewed by 2727
Abstract
Background: Nodular lymphocyte predominant Hodgkin lymphoma (NLPHL) is a rare variant of HL that accounts for 5% of all HL cases. The expression of CD20 on neoplastic lymphocytes provides a suitable target for novel treatments based on Rituximab. Due to its rarity, consolidated [...] Read more.
Background: Nodular lymphocyte predominant Hodgkin lymphoma (NLPHL) is a rare variant of HL that accounts for 5% of all HL cases. The expression of CD20 on neoplastic lymphocytes provides a suitable target for novel treatments based on Rituximab. Due to its rarity, consolidated and widely accepted treatment guidelines are still lacking for this disease. Methods: Between 1 December 2007 and 28 February 2018, sixteen consecutive newly diagnosed adult patients with NLPHL received Rituximab (induction ± maintenance)-based therapy, according to the baseline risk of German Hodgkin Study Group prognostic score system. The treatment efficacy and safety of the Rituximab-group were compared to those of a historical cohort of 12 patients with NLPHL who received Doxorubicin, Bleomycin, Vinblastine, Dacarbazine (ABVD) chemotherapy followed by radiotherapy (RT), if needed, according to a similar baseline risk. The primary outcome was progression-free survival (PFS) and secondary outcomes were overall survival (OS) and side-effects (according to the Common Terminology Criteria for Adverse Events, v4.03). Results: After a 7-year follow-up (range, 1–11 years), PFS was 100% for patients treated with the Rituximab-containing regimen versus 66% for patients of the historical cohort (p = 0.036). Four patients in the latter group showed insufficient response to therapy. The PFS for early favorable and early unfavorable NLPHLs was similar between treatment groups, while a better PFS was recorded for advanced-stages treated with the Rituximab-containing regimen. The OS was similar for the two treatment groups. Short- and long-term side-effects were more frequently observed in the historical cohort. Grade ≥3 neutropenia was more frequent in the historical cohort compared with the Rituximab-group (58.3% vs. 18.7%, respectively; p = 0.03). Long-term non-hematological toxicities were observed more frequently in the historical cohort. Conclusion: Our results confirm the value of Rituximab in NLPHL therapy and show that Rituximab (single-agent) induction and maintenance in a limited-stage, or Rituximab with ABVD only in the presence of risk factors, give excellent results while sparing cytotoxic agent- and/or RT-related damage. Furthermore, Rituximab inclusion in advanced-stage therapeutic strategy seems to improve PFS compared to conventional chemo-radiotherapy. Full article
(This article belongs to the Special Issue Recent Advances in Hodgkin’s Lymphoma)
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Review

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18 pages, 833 KiB  
Review
Immune Microenvironment Features and Dynamics in Hodgkin Lymphoma
by Clara Bertuzzi, Elena Sabattini and Claudio Agostinelli
Cancers 2021, 13(14), 3634; https://doi.org/10.3390/cancers13143634 - 20 Jul 2021
Cited by 11 | Viewed by 3007
Abstract
Classical Hodgkin’s lymphoma (cHL) accounts for 10% of all lymphoma diagnosis. The peculiar feature of the disease is the presence of large multinucleated Reed–Sternberg and mononuclear Hodgkin cells interspersed with a reactive microenvironment (ME). Due to the production of a large number of [...] Read more.
Classical Hodgkin’s lymphoma (cHL) accounts for 10% of all lymphoma diagnosis. The peculiar feature of the disease is the presence of large multinucleated Reed–Sternberg and mononuclear Hodgkin cells interspersed with a reactive microenvironment (ME). Due to the production of a large number of cytokines, Hodgkin cells (HCs) and Hodgkin Reed–Sternberg cells (HRSCs) attract and favour the expansion of different immune cell populations, modifying their functional status in order to receive prosurvival stimuli and to turn off the antitumour immune response. To this purpose HRSCs shape a biological niche by organizing the spatial distribution of cells in the ME. This review will highlight the contribution of the ME in the pathogenesis and prognosis of cHL and its role as a possible therapeutic target. Full article
(This article belongs to the Special Issue Recent Advances in Hodgkin’s Lymphoma)
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12 pages, 1906 KiB  
Review
Genomic Landscape of Hodgkin Lymphoma
by Magdalena M. Brune, Darius Juskevicius, Jasmin Haslbauer, Stefan Dirnhofer and Alexandar Tzankov
Cancers 2021, 13(4), 682; https://doi.org/10.3390/cancers13040682 - 8 Feb 2021
Cited by 15 | Viewed by 4562
Abstract
Background: Hodgkin lymphoma (HL) is predominantly composed of reactive, non-neoplastic cells surrounding scarcely distributed tumor cells, that is, so-called Hodgkin and Reed-Sternberg (HRS) or lymphocyte predominant (LP) cells. This scarcity impeded the analysis of the tumor cell genomes for a long time, but [...] Read more.
Background: Hodgkin lymphoma (HL) is predominantly composed of reactive, non-neoplastic cells surrounding scarcely distributed tumor cells, that is, so-called Hodgkin and Reed-Sternberg (HRS) or lymphocyte predominant (LP) cells. This scarcity impeded the analysis of the tumor cell genomes for a long time, but recently developed methods (especially laser capture microdissection, flow cytometry/fluorescence-activated cell sorting) facilitated molecular investigation, elucidating the pathophysiological principles of “Hodgkin lymphomagenesis”. Methods: We reviewed the relevant literature of the last three decades focusing on the genomic landscape of classic and nodular lymphocyte predominant HL (NLPHL) and summarized molecular cornerstones. Results: Firstly, the malignant cells of HL evade the immune system by altered expression of PDL1/2, B2M and MHC class I and II due to various genetic alterations. Secondly, tumor growth is promoted by permanently activated JAK/STAT signaling due to pervasive mutations of multiple genes involved in the pathway. Thirdly, apoptosis of neoplastic cells is prevented by alterations of NF-κB compounds and the PI3K/AKT/mTOR axis. Additionally, Epstein-Barr virus infection can simultaneously activate JAK/STAT and NF-κB, similarly leading to enhanced survival and evasion of apoptosis. Finally, epigenetic phenomena such as promoter hypermethylation lead to the downregulation of B-lineage-specific, tumor-suppressor and immune regulation genes. Conclusion: The blueprint of HL genomics has been laid, paving the way for future investigations into its complex pathophysiology. Full article
(This article belongs to the Special Issue Recent Advances in Hodgkin’s Lymphoma)
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20 pages, 2076 KiB  
Review
The Evolving Knowledge on T and NK Cells in Classic Hodgkin Lymphoma: Insights into Novel Subsets Populating the Immune Microenvironment
by Isacco Ferrarini, Antonella Rigo, Carlo Visco, Mauro Krampera and Fabrizio Vinante
Cancers 2020, 12(12), 3757; https://doi.org/10.3390/cancers12123757 - 14 Dec 2020
Cited by 12 | Viewed by 2803
Abstract
Classic Hodgkin lymphoma (cHL) is a unique lymphoid neoplasm characterized by extensive immune infiltrates surrounding rare malignant Hodgkin Reed–Sternberg (HRS) cells. Different subsets of T and NK cells have long been recognized in the cHL microenvironment, yet their distinct contribution to disease pathogenesis [...] Read more.
Classic Hodgkin lymphoma (cHL) is a unique lymphoid neoplasm characterized by extensive immune infiltrates surrounding rare malignant Hodgkin Reed–Sternberg (HRS) cells. Different subsets of T and NK cells have long been recognized in the cHL microenvironment, yet their distinct contribution to disease pathogenesis has remained enigmatic. Very recently, novel platforms for high dimensional analysis of immune cells, such as single-cell RNA sequencing and mass cytometry, have revealed unanticipated insights into the composition of T- and NK-cell compartments in cHL. Advances in imaging techniques have better defined specific T-helper subpopulations physically interacting with neoplastic cells. In addition, the identification of novel cytotoxic subsets with an exhausted phenotype, typically enriched in cHL milieu, is shedding light on previously unrecognized immune evasion mechanisms. This review examines the immunological features and the functional properties of T and NK subsets recently identified in the cHL microenvironment, highlighting their pathological interplay with HRS cells. We also discuss how this knowledge can be exploited to predict response to immunotherapy and to design novel strategies to improve PD-1 blockade efficacy. Full article
(This article belongs to the Special Issue Recent Advances in Hodgkin’s Lymphoma)
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