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Mature T-Cell and NK-Cell Neoplasms: A Global Landscape from Preclinical...
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Mature T-Cell and NK-Cell Neoplasms: A Global Landscape from Preclinical Models to Personalized, Biomarker-Driven Therapy

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

Deadline for manuscript submissions: closed (30 June 2023) | Viewed by 10607

Special Issue Editors

Prof. Dr. Pierluigi Porcu

E-Mail Website
Guest Editor
Sidney Kimmel Cancer Center at Jefferson, Philadelphia, PA, USA
Interests: biomarker discovery; targeted therapies; clinical trials
Dr. Stefan K Barta

E-Mail Website
Guest Editor
Hospital of the University of Pennsylvania, Philadelphia, PA, USA
Interests: mature NK/T cell lymphoma; biological therapies; cellular therapies; predictive and prognostic biomarkers; immunodeficiency associated lymphomas
Dr. Brad Haverkos

E-Mail Website
Guest Editor
Division of Hematology, University of Colorado, Aurora, CO 80045, USA
Interests: T- and NK-cell lymphomas; immunotherapy; Epstein-Barr virus

Special Issue Information

Dear Colleagues,

The global landscape of mature T-cell and NK-cell neoplasms has evolved and expanded dramatically over the past 5 years, as more and more data on genetic and epigenetic drivers, tumor microenvironment, key signaling molecules, and targetable pathways rapidly accrue, from the study of both preclinical models and from large-scale integrative molecular analyses of clinically annotated patient samples. Phase I trials of novel agents, increasingly consisting of mechanism-based combinations, are in progress, offering an exciting lineup of the new therapeutic options that are poised to cross the finish line of early clinical development and transition to Phase II validation. A number of prospective single arm Phase II and randomized Phase III studies have now completed accrual and reliable data are becoming available, finally providing an adequate if still incomplete evidence-based context to make better treatment decisions for patients and to generate new hypotheses for clinical trials. At the same time, several international registry studies have accrued large enough populations, with sufficient follow-up, to provide a valuable insight on patterns of care and outcomes for patients worldwide. Finally, tantalizing laboratory and clinical observations on the intricate genetic connections between normal and clonal hematopoiesis, T-cell development, and immune dysregulation are presenting a glimpse of what is certain to be a very complex picture of the early development of these malignancies.

This Special Issue of Cancers therefore encompasses new research articles and timely reviews on these key aspects of mature T-cell and NK-cell neoplasms with an emphasis on research being completed in the past 5 years and a focus on paradigm-changing studies.

Prof. Dr. Pierluigi Porcu
Dr. Stefan K Barta
Dr. Brad Haverkos
Guest Editors

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

  • Biomarkers
  • Novel therapies
  • Genetics
  • Preclinical
  • Microenvironment
  • Immunotherapy
  • Real world
  • Epidemiology

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Published Papers (3 papers)

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Review

24 pages, 439 KiB  
Review
Rational Targets of Therapy in Extranodal NK/T-Cell Lymphoma
by Ajay Major, Pierluigi Porcu and Bradley M. Haverkos
Cancers 2023, 15(5), 1366; https://doi.org/10.3390/cancers15051366 - 21 Feb 2023
Cited by 3 | Viewed by 2625
Abstract
Extranodal NK/T-cell lymphoma (ENKTL) is an aggressive extranodal non-Hodgkin lymphoma (NHL) with poor outcomes, particularly in advanced-stage and relapsed/refractory disease. Emerging research on molecular drivers of ENKTL lymphomagenesis by next-generation and whole genome sequencing has revealed diverse genomic mutations in multiple signaling pathways, [...] Read more.
Extranodal NK/T-cell lymphoma (ENKTL) is an aggressive extranodal non-Hodgkin lymphoma (NHL) with poor outcomes, particularly in advanced-stage and relapsed/refractory disease. Emerging research on molecular drivers of ENKTL lymphomagenesis by next-generation and whole genome sequencing has revealed diverse genomic mutations in multiple signaling pathways, with the identification of multiple putative targets for novel therapeutic agents. In this review, we summarize the biological underpinnings of newly-understood therapeutic targets in ENKTL with a focus on translational implications, including epigenetic and histone regulatory aberrations, activation of cell proliferation signaling pathways, suppression of apoptosis and tumor suppressor genes, changes in the tumor microenvironment, and EBV-mediated oncogenesis. In addition, we highlight prognostic and predictive biomarkers which may enable a personalized medicine approach toward ENKTL therapy. Full article
(This article belongs to the Special Issue Mature T-Cell and NK-Cell Neoplasms: A Global Landscape from Preclinical Models to Personalized, Biomarker-Driven Therapy)
21 pages, 1063 KiB  
Review
Central Nervous System Progression/Relapse in Mature T- and NK-Cell Lymphomas
by Rahul S. Bhansali and Stefan K. Barta
Cancers 2023, 15(3), 925; https://doi.org/10.3390/cancers15030925 - 1 Feb 2023
Cited by 3 | Viewed by 2373
Abstract
Non-Hodgkin lymphomas (NHL) are cancers of mature B-, T-, and NK-cells which display marked biological heterogeneity between different subtypes. Mature T- and NK-cell neoplasms are an often-aggressive subgroup of NHL and make up approximately 15% of all NHL. Long-term follow up studies have [...] Read more.
Non-Hodgkin lymphomas (NHL) are cancers of mature B-, T-, and NK-cells which display marked biological heterogeneity between different subtypes. Mature T- and NK-cell neoplasms are an often-aggressive subgroup of NHL and make up approximately 15% of all NHL. Long-term follow up studies have demonstrated that patients with relapsed/refractory disease have dismal outcomes; in particular, secondary central nervous system (CNS) involvement is associated with higher mortality, though it remains controversial whether this independently confers worse outcomes or if it simply reflects more aggressive systemic disease. Possible risk factors predictive of CNS involvement, such as an elevated lactate dehydrogenase and more than two sites of extranodal involvement, may suggest the latter, though several studies have suggested that discrete sites of anatomic involvement or tumor histology may be independent risk factors as well. Ultimately, small retrospective case series form the basis of our understanding of this rare but devastating event but have not yet demonstrated a consistent benefit of CNS-directed prophylaxis in preventing this outcome. Nonetheless, ongoing efforts are working to establish the epidemiology of CNS progression/relapse in mature T- and NK-cell lymphomas with the goal of identifying clinicopathologic risk factors, which may potentially help discern which patients may benefit from CNS-directed prophylactic therapy or more aggressive systemic therapy. Full article
(This article belongs to the Special Issue Mature T-Cell and NK-Cell Neoplasms: A Global Landscape from Preclinical Models to Personalized, Biomarker-Driven Therapy)
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17 pages, 749 KiB  
Review
Therapeutic Advances in Relapsed and Refractory Peripheral T-Cell Lymphoma
by Robert Stuver and Alison J. Moskowitz
Cancers 2023, 15(3), 589; https://doi.org/10.3390/cancers15030589 - 18 Jan 2023
Cited by 7 | Viewed by 4724
Abstract
Historic outcomes for patients with relapsed or refractory nodal-based T-cell lymphomas are poor, with survival generally measured in months in multiple reports from the late 20th and early 21st century. Until recently, salvage strategies have mostly been borrowed from other aggressive lymphomas. However, [...] Read more.
Historic outcomes for patients with relapsed or refractory nodal-based T-cell lymphomas are poor, with survival generally measured in months in multiple reports from the late 20th and early 21st century. Until recently, salvage strategies have mostly been borrowed from other aggressive lymphomas. However, dedicated investigations into the pathogenesis of T-cell lymphomas have resulted in an outpouring of therapies that target these diseases in biologically rational strategies. In particular, an evolving appreciation of the multiple complex oncogenic pathways and epigenetic changes that underlie these diseases has led to numerous agents targeting these aberrancies. Moreover, large reports of salvage allogeneic stem cell transplants in T-cell lymphoma have now been published, showing that adaptive immunotherapy is a potentially curative strategy for patients with relapsed or refractory disease. This review highlights therapeutic advances for relapsed or refractory T-cell lymphomas, including cellular therapy and allogeneic stem cell transplant, and provides a framework for management. Full article
(This article belongs to the Special Issue Mature T-Cell and NK-Cell Neoplasms: A Global Landscape from Preclinical Models to Personalized, Biomarker-Driven Therapy)
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