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Cancers
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T-Cell Lymphomas
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T-Cell Lymphomas

A special issue of Cancers (ISSN 2072-6694).

Deadline for manuscript submissions: closed (30 September 2021) | Viewed by 30784

Special Issue Editor

Prof. Dr. Pierre Brousset

E-Mail Website
Guest Editor
Department of Pathology, Institut Universitaire du Cancer de Toulouse Oncopole, 1 avenue Joliot-Curie, 31059 Toulouse Cedex, France
Interests: hematopathology; lymphoma; artificial intelligence; digital pathology; molecular genetics

Special Issue Information

Dear Colleagues,

T-cell lymphomas (TCLs) are rare and heterogeneous tumors that can be clinically localized or systemic. Systemic TCLs are characterized by a very poor prognosis and few therapeutic options are available despite recent hopes provided by the immunotherapy and targeted therapy. TCLs are distinct from B-cell lymphomas both in their pathophysiology and epidemiology. Immunological markers and molecular techniques have shed light on the mechanisms at play in their development but there is still a gap between the large number of mutated genes identified over the last ten years and their use as targets for patient treatments. The same holds true for B-cell lymphomas for which, for twenty years, anti-CD20 (Rituximab, Mabthera) antibodies have represented a major breakthrough in their treatment. Unfortunately, there is so far no equivalent of anti-CD20 antibodies to eradicate tumor cells in TCL. The next frontier in the understanding of the pathophysiology of TCL will be crossed by the use of integrated approaches based on data hybridization. A cross correlation of data obtained from clinics, imaging, and genomics (multiomics) will further our understanding of the biological mechanisms that could be targeted in the latter tumor type.

This Special Issue will highlight recent knowledge in the biology and clinical management of TCL. Different chapters will be proposed by experts in the field worldwide. This issue is also an occasion to emphasize the wide geographical, biological and clinical diversity of these mysterious tumors that develop from cells that are at the front line of the antitumor immune response. Therefore, the search for efficient therapeutic approaches in aggressive TCL remains as a catch 22 situation for the moment.

Prof. Dr. Pierre Brousset
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.

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

  • T-cell lymphoma
  • gene mutations
  • omics
  • data mining
  • targeted therapy
  • immunotherapy

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Published Papers (9 papers)

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Editorial

Jump to: Research, Review

4 pages, 449 KiB  
Editorial
Management of T-Cell Lymphoma: In Quest of the Holy Grail
by Sarah Péricart, Frédéric Escudié, David Grand and Pierre Brousset
Cancers 2021, 13(12), 2919; https://doi.org/10.3390/cancers13122919 - 11 Jun 2021
Viewed by 1516
Abstract
T-cell lymphomas (TCL) represent a very heterogeneous group of lymphoid tumors which are clearly distinct from B-cell neoplasms [...] Full article
(This article belongs to the Special Issue T-Cell Lymphomas)
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Research

Jump to: Editorial, Review

12 pages, 1663 KiB  
Article
RBMX Protein Expression in T-Cell Lymphomas Predicts Chemotherapy Response and Prognosis
by Franziska Lea Schümann, Marcus Bauer, Elisabeth Groß, Denis Terziev, Andreas Wienke, Claudia Wickenhauser, Mascha Binder and Thomas Weber
Cancers 2021, 13(19), 4788; https://doi.org/10.3390/cancers13194788 - 24 Sep 2021
Cited by 7 | Viewed by 2432
Abstract
T-cell non-Hodgkin’s lymphomas (T-NHL) are a heterogeneous group of lymphomas with a mature T-cell phenotype. While in some hematological diseases the prognosis improved over the last decades, T-NHL cases often relapse early or present with an initially refractory course. Recently, it has been [...] Read more.
T-cell non-Hodgkin’s lymphomas (T-NHL) are a heterogeneous group of lymphomas with a mature T-cell phenotype. While in some hematological diseases the prognosis improved over the last decades, T-NHL cases often relapse early or present with an initially refractory course. Recently, it has been shown that RNA binding proteins have a crucial role for malignant tumor initiation, progression and treatment response while contributing to chemotherapy resistance. Therefore, we investigated the protein expression of the RNA binding protein X (RBMX), which has been shown to be of great relevance in disease initiation and progression in hematological diseases in 53 T-NHL cases using conventional immunohistochemistry. Low RBMX expression was associated with better response to anthracycline-containing first-line treatment. Furthermore, low RBMX expression predicted an improved overall survival and progression-free survival in univariate analysis. Multivariable Cox regression revealed RBMX as an independent prognostic marker for overall survival (p = 0.007; hazard ratio (HR) = 0.204; 95% confidence interval (CI): 0.064–0.646) and progression-free survival (p = 0.006; HR = 0.235; 95% CI: 0.083–0.666). The study identifies low RBMX expression to predict better chemotherapy response, overall survival and progression-free survival in patients with T-cell non-Hodgkin’s lymphomas. These results suggest that RBMX protein expression levels might be a contributing factor towards chemotherapy resistance and thus affect prognosis. Hence, RBMX may be a potential therapeutic target and prognostic marker in T-cell lymphomas. Full article
(This article belongs to the Special Issue T-Cell Lymphomas)
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Review

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36 pages, 6388 KiB  
Review
Cellular Origins and Pathogenesis of Gastrointestinal NK- and T-Cell Lymphoproliferative Disorders
by Susan Swee-Shan Hue, Siok-Bian Ng, Shi Wang and Soo-Yong Tan
Cancers 2022, 14(10), 2483; https://doi.org/10.3390/cancers14102483 - 18 May 2022
Cited by 4 | Viewed by 3492
Abstract
The intestinal immune system, which must ensure appropriate immune responses to both pathogens and commensal microflora, comprises innate lymphoid cells and various T-cell subsets, including intra-epithelial lymphocytes (IELs). An example of innate lymphoid cells is natural killer cells, which may be classified into [...] Read more.
The intestinal immune system, which must ensure appropriate immune responses to both pathogens and commensal microflora, comprises innate lymphoid cells and various T-cell subsets, including intra-epithelial lymphocytes (IELs). An example of innate lymphoid cells is natural killer cells, which may be classified into tissue-resident, CD56bright NK-cells that serve a regulatory function and more mature, circulating CD56dim NK-cells with effector cytolytic properties. CD56bright NK-cells in the gastrointestinal tract give rise to indolent NK-cell enteropathy and lymphomatoid gastropathy, as well as the aggressive extranodal NK/T cell lymphoma, the latter following activation by EBV infection and neoplastic transformation. Conventional CD4+ TCRαβ+ and CD8αβ+ TCRαβ+ T-cells are located in the lamina propria and the intraepithelial compartment of intestinal mucosa as type ‘a’ IELs. They are the putative cells of origin for CD4+ and CD8+ indolent T-cell lymphoproliferative disorders of the gastrointestinal tract and intestinal T-cell lymphoma, NOS. In addition to such conventional T-cells, there are non-conventional T-cells in the intra-epithelial compartment that express CD8αα and innate lymphoid cells that lack TCRs. The central feature of type ‘b’ IELs is the expression of CD8αα homodimers, seen in monomorphic epitheliotropic intestinal T-cell lymphoma (MEITL), which primarily arises from both CD8αα+ TCRαβ+ and CD8αα+ TCRγδ+ IELs. EATL is the other epitheliotropic T-cell lymphoma in the GI tract, a subset of which arises from the expansion and reprograming of intracytoplasmic CD3+ innate lymphoid cells, driven by IL15 and mutations of the JAK-STAT pathway. Full article
(This article belongs to the Special Issue T-Cell Lymphomas)
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23 pages, 538 KiB  
Review
Peripheral T-Cell Lymphomas: Therapeutic Approaches
by David Sibon
Cancers 2022, 14(9), 2332; https://doi.org/10.3390/cancers14092332 - 8 May 2022
Cited by 12 | Viewed by 3667
Abstract
Peripheral T-cell lymphomas (PTCLs) are a heterogeneous group of rare neoplasms of mature T cells or natural killer (NK) cell. PTCLs usually have an aggressive course and a poor outcome. In recent years, significant progress has been made in the knowledge of the [...] Read more.
Peripheral T-cell lymphomas (PTCLs) are a heterogeneous group of rare neoplasms of mature T cells or natural killer (NK) cell. PTCLs usually have an aggressive course and a poor outcome. In recent years, significant progress has been made in the knowledge of the molecular lymphomagenesis of PTCLs, and through the development of new, more specific therapeutic molecules, one can hope in the coming years for more personalized medicine and improved patient prognosis. This review aims to provide an up-to-date overview of the current therapeutic approaches in nodal PTCLs. Full article
(This article belongs to the Special Issue T-Cell Lymphomas)
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14 pages, 5296 KiB  
Review
Peripheral T-Cell Lymphoma, Not Otherwise Specified: Clinical Manifestations, Diagnosis, and Future Treatment
by Stefano A. Pileri, Valentina Tabanelli, Stefano Fiori, Angelica Calleri, Federica Melle, Giovanna Motta, Daniele Lorenzini, Corrado Tarella and Enrico Derenzini
Cancers 2021, 13(18), 4535; https://doi.org/10.3390/cancers13184535 - 9 Sep 2021
Cited by 15 | Viewed by 2985
Abstract
Peripheral T-cell lymphoma, not otherwise specified (PTCL_NOS) corresponds to about one fourth of mature T-cell tumors, which overall represent 10–12% of all lymphoid malignancies. This category comprises all T-cell neoplasms, which do not correspond to any of the distinct entities listed in the [...] Read more.
Peripheral T-cell lymphoma, not otherwise specified (PTCL_NOS) corresponds to about one fourth of mature T-cell tumors, which overall represent 10–12% of all lymphoid malignancies. This category comprises all T-cell neoplasms, which do not correspond to any of the distinct entities listed in the WHO (World Health Organization) Classification of Tumours of Haematopoietic and Lymphoid Tissues. In spite of the extreme variability of morphologic features and phenotypic profiles, gene expression profiling (GEP) studies have shown a signature that is distinct from that of all remaining PTCLs. GEP has also allowed the identification of subtypes provided with prognostic relevance. Conversely to GEP, next-generation sequencing (NGS) has so far been applied to a limited number of cases, providing some hints to better understand the pathobiology of PTCL_NOS. Although several pieces of information have emerged from pathological studies, PTCL_NOS still remains a tumor with a dismal prognosis. The usage of CHOEP (cyclophosphamide, doxorubicin, vincristine, prednisone, etoposide) followed by autologous stem cell transplantation may represent the best option, by curing about 50% of the patients whom such an approach can be applied to. Many new drugs have been proposed without achieving the expected results. Thus, the optimal treatment of PTCL_NOS remains unidentified. Full article
(This article belongs to the Special Issue T-Cell Lymphomas)
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17 pages, 1686 KiB  
Review
Cytokines, Genetic Lesions and Signaling Pathways in Anaplastic Large Cell Lymphomas
by Jean-Philippe Merlio and Marshall E. Kadin
Cancers 2021, 13(17), 4256; https://doi.org/10.3390/cancers13174256 - 24 Aug 2021
Cited by 1 | Viewed by 2448
Abstract
ALCL is a tumor of activated T cells and possibly innate lymphoid cells with several subtypes according to clinical presentation and genetic lesions. On one hand, the expression of transcription factors and cytokine receptors triggers signaling pathways. On the other hand, ALCL tumor [...] Read more.
ALCL is a tumor of activated T cells and possibly innate lymphoid cells with several subtypes according to clinical presentation and genetic lesions. On one hand, the expression of transcription factors and cytokine receptors triggers signaling pathways. On the other hand, ALCL tumor cells also produce many proteins including chemokines, cytokines and growth factors that affect patient symptoms. Examples are accumulation of granulocytes stimulated by IL-8, IL-17, IL-9 and IL-13; epidermal hyperplasia and psoriasis-like skin lesions due to IL-22; and fever and weight loss in response to IL-6 and IFN-γ. In this review, we focus on the biology of the main ALCL subtypes as the identification of signaling pathways and ALCL-derived cytokines offers opportunities for targeted therapies. Full article
(This article belongs to the Special Issue T-Cell Lymphomas)
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16 pages, 3652 KiB  
Review
Epstein–Barr Virus-Associated T- and NK-Cell Lymphoproliferative Diseases: A Review of Clinical and Pathological Features
by Charlotte Syrykh, Sarah Péricart, Claire Lamaison, Frédéric Escudié, Pierre Brousset and Camille Laurent
Cancers 2021, 13(13), 3315; https://doi.org/10.3390/cancers13133315 - 1 Jul 2021
Cited by 20 | Viewed by 4415
Abstract
Epstein–Barr virus (EBV) is a ubiquitous virus detected in up to 95% of the general population. Most people are asymptomatic, while some may develop a wide range of EBV-associated lymphoproliferative disorders (LPD). Among them, EBV-positive T/NK LPD are uncommon diseases defined by the [...] Read more.
Epstein–Barr virus (EBV) is a ubiquitous virus detected in up to 95% of the general population. Most people are asymptomatic, while some may develop a wide range of EBV-associated lymphoproliferative disorders (LPD). Among them, EBV-positive T/NK LPD are uncommon diseases defined by the proliferation of T- or NK-cells infected by EBV. The 2017 World Health Organization (WHO) classification recognizes the following entities characterized by different outcomes: chronic active EBV infection of T- or NK-cell types (cutaneous and systemic forms), systemic EBV-positive T-cell lymphoma of childhood, EBV-positive aggressive NK-cell leukemia, extra nodal NK/T-cell lymphoma nasal type, and the new provisional entity known as primary EBV-positive nodal T/NK-cell lymphoma. In addition, EBV associated-hemophagocytic lymphohistiocytosis is part of EBV-positive T/NK LPD, but has not been included in the WHO classification due to its reactive nature. Despite novel insights from high-throughput molecular studies, EBV-positive NK/T-cell LPD diagnoses remain challenging, especially because of their rarity and overlap. Until now, an accurate EBV-positive NK/T LPD diagnosis has been based on its clinical presentation and course correlated with its histological features. This review aims to summarize clinical, pathological and molecular features of EBV-positive T/NK LPD subtypes and to provide an overview of new understandings regarding these rare disorders. Full article
(This article belongs to the Special Issue T-Cell Lymphomas)
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24 pages, 1146 KiB  
Review
Mycosis Fungoides and Sézary Syndrome: An Integrative Review of the Pathophysiology, Molecular Drivers, and Targeted Therapy
by Nuria García-Díaz, Miguel Ángel Piris, Pablo Luis Ortiz-Romero and José Pedro Vaqué
Cancers 2021, 13(8), 1931; https://doi.org/10.3390/cancers13081931 - 16 Apr 2021
Cited by 30 | Viewed by 5865
Abstract
Primary cutaneous T-cell lymphomas (CTCLs) constitute a heterogeneous group of diseases that affect the skin. Mycosis fungoides (MF) and Sézary syndrome (SS) account for the majority of these lesions and have recently been the focus of extensive translational research. This review describes and [...] Read more.
Primary cutaneous T-cell lymphomas (CTCLs) constitute a heterogeneous group of diseases that affect the skin. Mycosis fungoides (MF) and Sézary syndrome (SS) account for the majority of these lesions and have recently been the focus of extensive translational research. This review describes and discusses the main pathobiological manifestations of MF/SS, the molecular and clinical features currently used for diagnosis and staging, and the different therapies already approved or under development. Furthermore, we highlight and discuss the main findings illuminating key molecular mechanisms that can act as drivers for the development and progression of MF/SS. These seem to make up an orchestrated constellation of genomic and environmental alterations generated around deregulated T-cell receptor (TCR)/phospholipase C, gamma 1, (PLCG1) and Janus kinase/ signal transducer and activator of transcription (JAK/STAT) activities that do indeed provide us with novel opportunities for diagnosis and therapy. Full article
(This article belongs to the Special Issue T-Cell Lymphomas)
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15 pages, 1030 KiB  
Review
Clinical Applications of Genomic Alterations in ATLL: Predictive Markers and Therapeutic Targets
by Noriaki Yoshida, Hiroaki Miyoshi and Koichi Ohshima
Cancers 2021, 13(8), 1801; https://doi.org/10.3390/cancers13081801 - 9 Apr 2021
Cited by 7 | Viewed by 2627
Abstract
Adult T-cell leukemia/lymphoma (ATLL) is a peripheral T-cell lymphoma (PTCL) caused by human T-cell leukemia virus type 1 (HTLV-1). Recent comprehensive genomic analyses have revealed the genomic landscape. One of the important findings of genomic alterations in ATLL is that almost all alterations [...] Read more.
Adult T-cell leukemia/lymphoma (ATLL) is a peripheral T-cell lymphoma (PTCL) caused by human T-cell leukemia virus type 1 (HTLV-1). Recent comprehensive genomic analyses have revealed the genomic landscape. One of the important findings of genomic alterations in ATLL is that almost all alterations are subclonal, suggesting that therapeutic strategies targeting a genomic alteration will result in partial effects. Among the identified alterations, genes involved in T-cell receptor signaling and immune escape mechanisms, such as PLCG1, CARD11, and PD-L1 (also known as CD274), are characteristic of ATLL alterations. From a geographic perspective, ATLL patients in Caribbean islands tend to be younger than those in Japan and the landscape differs between the two areas. Additionally, young Japanese ATLL patients frequently have CD28 fusions, compared with unselected Japanese cases. From a clinical perspective, PD-L1 amplification is an independent prognostic factor among every subtype of ATLL case. Recently, genomic analysis using deep sequencing identified a pre-ATLL clone with ATLL-common mutations in HTLV-1 carriers before development, indicating that genomic analysis can stratify cases based on the risks of development and mortality. In addition to genomic alterations, targetable super-enhancers have been identified in ATLL. These data can be leveraged to improve the prognosis of ATLL. Full article
(This article belongs to the Special Issue T-Cell Lymphomas)
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