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Cancers
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Immunology of Hodgkin Lymphoma
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Immunology of Hodgkin Lymphoma

A special issue of Cancers (ISSN 2072-6694). This special issue belongs to the section "Cancer Immunology and Immunotherapy".

Deadline for manuscript submissions: closed (31 January 2023) | Viewed by 11944

Special Issue Editor

Dr. Arjan Diepstra

E-Mail Website
Guest Editor
Department of Pathology and Medical Biology, University of Groningen, University Medical Centre Groningen, 9700 RB Groningen, The Netherlands
Interests: Hodgkin lymphoma; immunology; antigen presentation; biomarkers; genetic susceptibility

Special Issue Information

Dear Colleagues,

Hodgkin Lymphoma (HL) is a cancer of lymph nodes and is commonly diagnosed in adolescents and young adults. It is characterized by a minority of tumor cells, called Hodgkin and Reed–Sternberg (HRS) cells, that are surrounded by a large number of reactive immune cells. The HRS cells originate from germinal center B-cells and are highly aberrant. It is hard to understand how they can develop within lymph nodes, especially in young and otherwise healthy individuals. This is even more apparent in cases in which the immunogenic Epstein–Barr-virus (EBV) is present in the tumor cells. Not only do (precursor) HRS cells escape from a multitude of anti-tumor immune responses, they even shape and hijack the tumor microenvironment (TME) for their own benefit. This may explain why novel treatments like immune checkpoint inhibitors that target the TME are highly effective in HL. However, despite advancements in the past decades, much has still to be learned on the immunology of HL and its role in susceptibility, pathogenesis, and treatment response.

You are invited to contribute original research to this Special Issue on the Immunology of Hodgkin Lymphoma. The main theme is the cross-talk between (cells of) the TME and (precursor) HRS cells. Manuscripts on immunology related blood biomarkers and genetic susceptibility are also invited.

Dr. Arjan Diepstra
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 short 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.

Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 2900 CHF (Swiss Francs). Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

  • Hodgkin Lymphoma
  • immunology
  • tumor microenvironment
  • Epstein–Barr virus
  • pathogenesis
  • susceptibility
  • biomarkers

Published Papers (4 papers)

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Research

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14 pages, 1024 KiB  
Article
Increased Production of B-Cell Activating Cytokines and Altered Peripheral B-Cell Subset Distribution during HIV-Related Classical Hodgkin Lymphoma
by Raphael Lievin, Houria Hendel-Chavez, Aliou Baldé, Rémi Lancar, Michèle Algarte-Génin, Roman Krzysiek, Dominique Costagliola, Lambert Assoumou, Yassine Taoufik and Caroline Besson
Cancers 2022, 14(1), 128; https://0-doi-org.brum.beds.ac.uk/10.3390/cancers14010128 - 28 Dec 2021
Cited by 2 | Viewed by 1883
Abstract
Classical Hodgkin Lymphoma incidence increases in HIV-1-infected patients (HIV-cHL). HIV infection is associated with higher B-cell activation. Here, in 38 HIV-cHL patients from the French cohort ANRS-CO16 Lymphovir, we examined longitudinally over 24 months the serum levels of the B-cell activating cytokines IL10, [...] Read more.
Classical Hodgkin Lymphoma incidence increases in HIV-1-infected patients (HIV-cHL). HIV infection is associated with higher B-cell activation. Here, in 38 HIV-cHL patients from the French cohort ANRS-CO16 Lymphovir, we examined longitudinally over 24 months the serum levels of the B-cell activating cytokines IL10, IL6, and BAFF, and blood distribution of B-cell subsets. Fourteen HIV-cHL patients were also compared to matched HIV-infected controls without cHL. IL10, IL6, and BAFF levels were higher in HIV-cHL patients than in controls (p < 0.0001, p = 0.002, and p < 0.0001, respectively). Cytokine levels increased in patients with advanced-stage lymphoma compared to those with limited-stage (p = 0.002, p = 0.03, and p = 0.01, respectively). Cytokine levels significantly decreased following HIV-cHL diagnosis and treatment. Blood counts of whole B-cells were similar in HIV-cHL patients and controls, but the distribution of B-cell subsets was different with higher ratios of naive B-cells over memory B-cells in HIV-cHL patients. Blood accumulation of naive B-cells was more marked in patients with advanced cHL stages (p = 0.06). During the follow-up, total B-cell counts increased (p < 0.0001), and the proportion of naive B-cells increased further (p = 0.04). Together the results suggest that in HIV-infected patients, cHL is associated with a particular B-cell-related environment that includes increased production of B-cell-activating cytokines and altered peripheral distribution of B-cell subsets. This B-cell-related environment may fuel the process of tumorigenesis. Full article
(This article belongs to the Special Issue Immunology of Hodgkin Lymphoma)
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10 pages, 3062 KiB  
Article
HLA Expression in Relation to HLA Type in Classic Hodgkin Lymphoma Patients
by Geok Wee Tan, Peijia Jiang, Ilja M. Nolte, Kushi Kushekhar, Rianne N. Veenstra, Bouke G. Hepkema, Ruth F. Jarrett, Anke van den Berg and Arjan Diepstra
Cancers 2021, 13(22), 5833; https://0-doi-org.brum.beds.ac.uk/10.3390/cancers13225833 - 20 Nov 2021
Cited by 1 | Viewed by 2367
Abstract
Several human leukocyte antigen (HLA) alleles are strongly associated with susceptibility to classic Hodgkin lymphoma (cHL), also in subgroups stratified for presence of the Epstein–Barr virus (EBV). We tested the hypothesis that the pressure on cHL tumour cells to lose HLA expression is [...] Read more.
Several human leukocyte antigen (HLA) alleles are strongly associated with susceptibility to classic Hodgkin lymphoma (cHL), also in subgroups stratified for presence of the Epstein–Barr virus (EBV). We tested the hypothesis that the pressure on cHL tumour cells to lose HLA expression is associated with HLA susceptibility alleles. A meta-analysis was carried out to identify consistent protective and risk HLA alleles in a combined cohort of 839 cHL patients from the Netherlands and the United Kingdom. Tumour cell HLA expression was studied in 338 cHL cases from these two cohorts and correlated to the presence of specific susceptibility HLA alleles. Carriers of the HLA-DRB1*07 protective allele frequently lost HLA class II expression in cHL overall. Patients carrying the HLA-DRB1*15/16 (DR2) risk allele retained HLA class II expression in EBV− cHL and patients with the HLA-B*37 risk allele retained HLA class I expression more frequently than non-carriers in EBV+ cHL. The other susceptibility alleles showed no significant differences in expression. Thus, HLA expression by tumour cells is associated with a subset of the protective and risk alleles. This strongly suggests that HLA associations in cHL are related to peptide binding capacities of specific HLA alleles. Full article
(This article belongs to the Special Issue Immunology of Hodgkin Lymphoma)
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Review

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25 pages, 6004 KiB  
Review
Current and Emerging Approaches to Study Microenvironmental Interactions and Drug Activity in Classical Hodgkin Lymphoma
by Naike Casagrande, Cinzia Borghese and Donatella Aldinucci
Cancers 2022, 14(10), 2427; https://0-doi-org.brum.beds.ac.uk/10.3390/cancers14102427 - 14 May 2022
Cited by 1 | Viewed by 2295
Abstract
Classic Hodgkin lymphoma is characterized by a few tumor cells surrounded by a protective and immunosuppressive tumor microenvironment (TME) composed by a wide variety of noncancerous cells that are an active part of the disease. Therefore, new techniques to study the cHL-TME and [...] Read more.
Classic Hodgkin lymphoma is characterized by a few tumor cells surrounded by a protective and immunosuppressive tumor microenvironment (TME) composed by a wide variety of noncancerous cells that are an active part of the disease. Therefore, new techniques to study the cHL-TME and new therapeutic strategies targeting specifically tumor cells, reactivating the antitumor immunity, counteracting the protective effects of the TME, were developed. Here, we describe new methods used to study the cell composition, the phenotype, and the spatial distribution of Hodgkin and Reed–Sternberg (HRS) cells and of noncancerous cells in tumor tissues. Moreover, we propose a classification, with increasing complexity, of the in vitro functional studies used to clarify the interactions leading not only to HRS cell survival, growth and drug resistance, but also to the immunosuppressive tumor education of monocytes, T lymphocytes and fibroblasts. This classification also includes new 3-dimensional (3D) models, obtained by cultivating HRS cells in extracellular matrix scaffolds or in sponge scaffolds, under non-adherent conditions with noncancerous cells to form heterospheroids (HS), implanted in developing chick eggs (ovo model). We report results obtained with these approaches and their applications in clinical setting. Full article
(This article belongs to the Special Issue Immunology of Hodgkin Lymphoma)
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22 pages, 1926 KiB  
Review
The Hodgkin Lymphoma Immune Microenvironment: Turning Bad News into Good
by Victoria Menéndez, José L. Solórzano, Sara Fernández, Carlos Montalbán and Juan F. García
Cancers 2022, 14(5), 1360; https://0-doi-org.brum.beds.ac.uk/10.3390/cancers14051360 - 7 Mar 2022
Cited by 16 | Viewed by 4460
Abstract
The classic Hodgkin lymphoma (cHL) tumor microenvironment (TME) is by far the most abundant component of tumors and is responsible for most of their biological and clinical characteristics. Recent advances in our knowledge of these networks in cellular interactions allow us to understand [...] Read more.
The classic Hodgkin lymphoma (cHL) tumor microenvironment (TME) is by far the most abundant component of tumors and is responsible for most of their biological and clinical characteristics. Recent advances in our knowledge of these networks in cellular interactions allow us to understand that the neoplastic Hodgkin and Reed Sternberg (HRS) cells, although they are in the minority, are the main architects of this dysregulated immune milieu. Here, we review the major changes that have happened in recent years: from TME as a helpless bystander, reflecting an ineffective immune response, to a dynamic tumor-promoting and immunosuppressive element. The HRS cells promote survival through interconnected intrinsic and extrinsic alterations, boosting pro-tumoral signaling pathways through genetic aberrations and autocrine growth signals, in parallel with abnormal cytokine secretion for the recruitment and selection of the best cell partners for this immunosuppressive TME. In turn, cHL is already proving to be the perfect model with which to address an immune checkpoint blockade. Preliminary data demonstrate the utility of druggable key signaling pathways in this ensemble, such as JAK-STAT, NF-κB, and others. In addition, myriad biomarkers predicting a response await validation by new in situ multiplex analytical methods, single-cell gene expression, and other techniques. Together, these components will define the functional phenotypes with which we will elucidate the molecular pathogenesis of the disease and improve the survival of patients who are refractory to conventional therapies. Full article
(This article belongs to the Special Issue Immunology of Hodgkin Lymphoma)
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