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Molecular Pathology and Immunotherapy of Lymphoma
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Molecular Pathology and Immunotherapy of Lymphoma

A special issue of International Journal of Molecular Sciences (ISSN 1422-0067). This special issue belongs to the section "Molecular Pathology, Diagnostics, and Therapeutics".

Deadline for manuscript submissions: closed (25 January 2024) | Viewed by 7155

Special Issue Editor

Dr. Monica Civallero

E-Mail Website
Guest Editor
Department CHIMOMO, University of Modena and Reggio Emilia, Via del Pozzo 71, 41124 Modena, Italy
Interests: T-cell lymphoma

Special Issue Information

Dear Colleagues,

Lymphomas are a large group of malignancies involving lymphoid tissues, and are divided into two large subgroups: Hodgkin's lymphoma (HL) and non-Hodgkin's lymphomas (NHL). CAR-T therapy and immune checkpoint inhibitors have been introduced in the clinical practice of malignant lymphomas. On the other hand, there are many histopathological subtypes that cannot directly receive the benefits of immunotherapy, and sufficient improvement in the prognosis of these subtypes is not observed.

Over the past decade, advances in high-throughput sequencing technologies have provided a wealth of information on the role of both genomic and epigenomic deregulations in the malignant transformation and pathophysiology of B- and T-lymphoid malignancies. A broad range of genetic alterations are now incorporated into World Health Organization-defined criteria for the diagnostic evaluation of patients with lymphoid malignancies. Future advances in molecular methods will enable the expansion of the knowledge of lymphomagenesis by increasing the variety of tools used in daily clinical practice, including diagnosis, risk stratification, identification of therapeutic targets, treatment resistance, and the determination of minimal measures of residual disease in lymphomas. By carrying this out, each patient will be provided with more effective treatments with fewer side effects and with the ultimate goal of prolonging survival and/or curing the disease.

Dr. Monica Civallero
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. International Journal of Molecular Sciences is an international peer-reviewed open access semimonthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. There is an Article Processing Charge (APC) for publication in this open access journal. For details about the APC please see here. 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

  • lymphoma diagnostics
  • immunotherapy
  • molecular diagnostics
  • non-Hodgkin lymphoma
  • sequencing

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Published Papers (4 papers)

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Research

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25 pages, 4377 KiB  
Article
Insight into Mantle Cell Lymphoma Pathobiology, Diagnosis, and Treatment Using Network-Based and Drug-Repurposing Approaches
by Georgia Orfanoudaki, Konstantina Psatha and Michalis Aivaliotis
Int. J. Mol. Sci. 2024, 25(13), 7298; https://doi.org/10.3390/ijms25137298 - 2 Jul 2024
Cited by 1 | Viewed by 1342
Abstract
Mantle cell lymphoma (MCL) is a rare, incurable, and aggressive B-cell non-Hodgkin lymphoma (NHL). Early MCL diagnosis and treatment is critical and puzzling due to inter/intra-tumoral heterogeneity and limited understanding of the underlying molecular mechanisms. We developed and applied a multifaceted analysis of [...] Read more.
Mantle cell lymphoma (MCL) is a rare, incurable, and aggressive B-cell non-Hodgkin lymphoma (NHL). Early MCL diagnosis and treatment is critical and puzzling due to inter/intra-tumoral heterogeneity and limited understanding of the underlying molecular mechanisms. We developed and applied a multifaceted analysis of selected publicly available transcriptomic data of well-defined MCL stages, integrating network-based methods for pathway enrichment analysis, co-expression module alignment, drug repurposing, and prediction of effective drug combinations. We demonstrate the “butterfly effect” emerging from a small set of initially differentially expressed genes, rapidly expanding into numerous deregulated cellular processes, signaling pathways, and core machineries as MCL becomes aggressive. We explore pathogenicity-related signaling circuits by detecting common co-expression modules in MCL stages, pointing out, among others, the role of VEGFA and SPARC proteins in MCL progression and recommend further study of precise drug combinations. Our findings highlight the benefit that can be leveraged by such an approach for better understanding pathobiology and identifying high-priority novel diagnostic and prognostic biomarkers, drug targets, and efficacious combination therapies against MCL that should be further validated for their clinical impact. Full article
(This article belongs to the Special Issue Molecular Pathology and Immunotherapy of Lymphoma)
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10 pages, 452 KiB  
Article
Serum-Soluble CD163 Levels as a Prognostic Biomarker in Patients with Diffuse Large B-Cell Lymphoma Treated with Chemoimmunotherapy
by Aspasia Koudouna, Annita Ioanna Gkioka, Alexandros Gkiokas, Thomai M. Tryfou, Mavra Papadatou, Alexandros Alexandropoulos, Vassiliki Bartzi, Nikolitsa Kafasi and Marie-Christine Kyrtsonis
Int. J. Mol. Sci. 2024, 25(5), 2862; https://doi.org/10.3390/ijms25052862 - 1 Mar 2024
Cited by 3 | Viewed by 1158
Abstract
The majority of patients with Diffuse Large B-cell Lymphoma (DLBCL) will respond to first-line treatment and be cured. However, the disease is heterogeneous, and biomarkers able to discriminate patients with suboptimal prognosis are needed. M2 CD163-positive tumor-associated macrophages (TAMs) were shown to be [...] Read more.
The majority of patients with Diffuse Large B-cell Lymphoma (DLBCL) will respond to first-line treatment and be cured. However, the disease is heterogeneous, and biomarkers able to discriminate patients with suboptimal prognosis are needed. M2 CD163-positive tumor-associated macrophages (TAMs) were shown to be implicated in DLBCL disease activity regulation. Serum-soluble CD163 (sCD163) functions as a scavenger receptor for haptoglobin–hemoglobin complexes and is mostly expressed by monocytes and macrophages. Its levels are used to determine macrophage activation. We aimed to determine serum sCD163 in a sample of DLBCL patients and study eventual correlations with parameters of disease activity or survival. Serum sCD163 levels were measured in 40 frozen sera from patients diagnosed with DLBCL and 30 healthy individuals (HIs) using an enzyme-linked immunosorbent assay (ELISA). Statistical analyses were performed using SPSS version 28. The results showed that patients who achieved complete response after standard-of-care immunochemotherapy and were alive and disease-free after 12 months of follow-up but had elevated sCD163 levels (above median) at diagnosis presented a significantly worse overall survival compared to those with initial serum sCD163 levels below the median (p = 0.03). Consequently, serum sCD163 levels in patients with DLBCL may constitute a marker of long-term response to chemoimmunotherapy. Full article
(This article belongs to the Special Issue Molecular Pathology and Immunotherapy of Lymphoma)
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16 pages, 3355 KiB  
Article
Pathogenic Variants Associated with Epigenetic Control and the NOTCH Pathway Are Frequent in Classic Hodgkin Lymphoma
by Antonio Santisteban-Espejo, Irene Bernal-Florindo, Pedro Montero-Pavon, Jose Perez-Requena, Lidia Atienza-Cuevas, Maria del Carmen Fernandez-Valle, Ana Villalba-Fernandez and Marcial Garcia-Rojo
Int. J. Mol. Sci. 2024, 25(5), 2457; https://doi.org/10.3390/ijms25052457 - 20 Feb 2024
Cited by 1 | Viewed by 1467
Abstract
Classic Hodgkin lymphoma (cHL) constitutes a B-cell neoplasm derived from germinal center lymphocytes. Despite high cure rates (80–90%) obtained with the current multiagent protocols, a significant proportion of cHL patients experience recurrences, characterized by a lower sensitivity to second-line treatments. The genomic background [...] Read more.
Classic Hodgkin lymphoma (cHL) constitutes a B-cell neoplasm derived from germinal center lymphocytes. Despite high cure rates (80–90%) obtained with the current multiagent protocols, a significant proportion of cHL patients experience recurrences, characterized by a lower sensitivity to second-line treatments. The genomic background of chemorefractory cHL is still poorly understood, limiting personalized treatment strategies based on molecular features. In this study, using a targeted next-generation sequencing (NGS) panel specifically designed for cHL research, we compared chemosensitive and chemorefractory diagnostic tissue samples of cHL patients. Furthermore, we longitudinally examined paired diagnosis–relapsesamples of chemorefractory cHL in order to define patterns of dynamic evolution and clonal selection. Pathogenic variants in NOTCH1 and NOTCH2 genes frequently arise in cHL. Mutations in genes associated with epigenetic regulation (CREBBP and EP300) are particularly frequent in relapsed/refractory cHL. The appearance of novel clones characterized by mutations previously not identified at diagnosis is a common feature in cHL cases showing chemoresistance to frontline treatments. Our results expand current molecular and pathogenic knowledge of cHL and support the performance of molecular studies in cHL prior to the initiation of first-line therapies. Full article
(This article belongs to the Special Issue Molecular Pathology and Immunotherapy of Lymphoma)
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Review

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23 pages, 1578 KiB  
Review
Immune Cytolytic Activity and Strategies for Therapeutic Treatment
by Stephanie Agioti and Apostolos Zaravinos
Int. J. Mol. Sci. 2024, 25(7), 3624; https://doi.org/10.3390/ijms25073624 - 23 Mar 2024
Cited by 1 | Viewed by 2537
Abstract
Intratumoral immune cytolytic activity (CYT), calculated as the geometric mean of granzyme-A (GZMA) and perforin-1 (PRF1) expression, has emerged as a critical factor in cancer immunotherapy, with significant implications for patient prognosis and treatment outcomes. Immune checkpoint pathways, the composition of the tumor [...] Read more.
Intratumoral immune cytolytic activity (CYT), calculated as the geometric mean of granzyme-A (GZMA) and perforin-1 (PRF1) expression, has emerged as a critical factor in cancer immunotherapy, with significant implications for patient prognosis and treatment outcomes. Immune checkpoint pathways, the composition of the tumor microenvironment (TME), antigen presentation, and metabolic pathways regulate CYT. Here, we describe the various methods with which we can assess CYT. The detection and analysis of tumor-infiltrating lymphocytes (TILs) using flow cytometry or immunohistochemistry provide important information about immune cell populations within the TME. Gene expression profiling and spatial analysis techniques, such as multiplex immunofluorescence and imaging mass cytometry allow the study of CYT in the context of the TME. We discuss the significant clinical implications that CYT has, as its increased levels are associated with positive clinical outcomes and a favorable prognosis. Moreover, CYT can be used as a prognostic biomarker and aid in patient stratification. Altering CYT through the different methods targeting it, offers promising paths for improving treatment responses. Overall, understanding and modulating CYT is critical for improving cancer immunotherapy. Research into CYT and the factors that influence it has the potential to transform cancer treatment and improve patient outcomes. Full article
(This article belongs to the Special Issue Molecular Pathology and Immunotherapy of Lymphoma)
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