Treatment of Peripheral T-cell Lymphomas

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

Deadline for manuscript submissions: 15 October 2025 | Viewed by 5409

Special Issue Editor


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Guest Editor
Department of Hematology and Medical Oncology, University of Göttingen, 37075 Gottingen, Germany
Interests: T-cell lymphoma; molecular targets; targeted therapy; biomarker

Special Issue Information

Dear Colleagues,

Peripheral T-cell lymphomas (PTCL) are a clinically and molecularly highly heterogeneous group of rare lymphoid malignancies, that typically share an aggressive clinical behavior and poor prognosis. With current first-line treatment strategies, only a minority of patients can be cured and relapsed-refractory diseases underscore the need for innovative therapeutic strategies.

Over the past decade, molecular studies unraveled distinct pathogenic alterations in subgroups of PTCL, providing a basis for both molecular classification and specific therapies addressing the pivotal biology of these diseases. Indeed, upcoming concepts including targeted inhibitors of crucial oncogenic signaling pathways, epigenetic therapeutics as well as immunotherapeutic approaches show promise. Still, tailoring optimal concepts for patients with PTCL remains a significant challenge.

This special issue will highlight preclinical and clinical research on therapeutic strategies and biomarkers in PTCL.

Dr. Raphael Koch
Guest Editor

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Keywords

  • T-cell lymphoma
  • PTCL
  • molecular targets
  • targeted therapy
  • immunotherapy
  • combination therapy
  • biomarker

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Published Papers (4 papers)

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Research

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15 pages, 3520 KiB  
Article
FoxP3+ Regulatory T-Cell Quantities in Nodal T-Follicular Helper Cell Lymphomas and Peripheral T-Cell Lymphomas Not Otherwise Specified and Their Impact on Overall Survival
by Eva Erzar, Alexandar Tzankov, Janja Ocvirk, Biljana Grčar Kuzmanov, Lučka Boltežar, Veronika Kloboves Prevodnik and Gorana Gašljević
Cancers 2024, 16(23), 4011; https://doi.org/10.3390/cancers16234011 - 29 Nov 2024
Viewed by 747
Abstract
Background/Objectives: The tumour microenvironment (TME) plays an important role in the development and progression of cancer and it differs among lymphomas, both with respect to the composition and quantity of specific tumour-infiltrating immune cells (TICs), such as FoxP3+ regulatory T cells (Tregs). [...] Read more.
Background/Objectives: The tumour microenvironment (TME) plays an important role in the development and progression of cancer and it differs among lymphomas, both with respect to the composition and quantity of specific tumour-infiltrating immune cells (TICs), such as FoxP3+ regulatory T cells (Tregs). The role of FoxP3+ Tregs in the TME of peripheral T-cell lymphomas (PTCLs) is complex, and their impact on overall survival (OS) remains unclear. Consequently, we aim to evaluate and compare the FoxP3+ cell quantity in nodal PTCLs and reactive lymph nodes (LNs), with a focus on investigating their impact on OS. Methods: excisional lymph node (LN) biopsies from 105 nodal PTCLs and 17 reactive LNs are immunohistochemically stained for FoxP3. Visual scoring of FoxP3+ cells is performed, and different cut-off values are used to evaluate the impact of FoxP3+ cell quantity on OS. Results: FoxP3+ cells are present in the TME of all cases, except for four cases where FoxP3+ is expressed in lymphoma cells. Lower FoxP3+ cell quantities are observed in certain nodal PTCL subtypes compared to reactive LNs. Patients with high FoxP3+ cell quantities show improved OS. However, the FoxP3+ cell quantity is not confirmed as an independent prognostic biomarker. Conclusions: these findings underscore the promise of FoxP3+ cell quantities as added value in prognosis and highlight the potential benefits of Treg-stimulating therapies in PTCLs. Full article
(This article belongs to the Special Issue Treatment of Peripheral T-cell Lymphomas)
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13 pages, 669 KiB  
Article
PTCY-Based Haploidentical Donor Transplantation versus HLA-Matched Related and Unrelated Donor Transplantations in Patients with Refractory or Relapsed Lymphoma—A Matched-Pair Analysis
by Sarah Haebe, Alessia Fraccaroli, Elena Stauffer, Dusan Prevalsek, Anna K. Zoellner, Heidrun Drolle, Hans-Joachim Stemmler, Martin Dreyling, Michael von Bergwelt-Baildon and Johanna Tischer
Cancers 2023, 15(21), 5246; https://doi.org/10.3390/cancers15215246 - 31 Oct 2023
Cited by 1 | Viewed by 1422
Abstract
Allogeneic hematopoietic stem cell transplantation (allo-HSCT) has demonstrated its potential as a curative option for patients with r/r lymphoma. With the introduction of post-transplant cyclophosphamide-based (PTCY) graft-versus-host disease (GvHD) prophylaxis, allo-HCT using haploidentical related donors (Haplo-HSCT) has emerged as a valuable alternative for [...] Read more.
Allogeneic hematopoietic stem cell transplantation (allo-HSCT) has demonstrated its potential as a curative option for patients with r/r lymphoma. With the introduction of post-transplant cyclophosphamide-based (PTCY) graft-versus-host disease (GvHD) prophylaxis, allo-HCT using haploidentical related donors (Haplo-HSCT) has emerged as a valuable alternative for patients without an available HLA-matched donor. In this study, we compared intermediate and long-term outcomes between Haplo-HSCT and HLA-matched related donor (MRD) and unrelated donor (URD) transplantations in 16 matched pairs using age, disease status, lymphoma classification and performance status as matching criteria. Of note, 88% of patients in each group presented with active disease at the time of conditioning. After a median follow-up of >10 years, 10-year overall and progression-free survival and non-relapse mortality incidence after Haplo-HSCT were 31%, 25% and 38%, respectively, and did not differ compared to the values observed in MRD-HSCT and URD-HSCT. A remarkable lower incidence of acute GvHD ≥ II and moderate and severe chronic GvHD was observed after Haplo-HSCT compared to MRD-HSCT (50%/50%, p = 0.03/0.03) and URD-HSCT (44%/38%, p = 0.04/0.08), resulting in slightly higher 10-year GvHD-free and relapse-free survival (25%) and chronic GvHD-free and relapse-free survival (25%) in the Haplo-HSCT group. In conclusion, Haplo-HSCT is an effective treatment in patients with non-remission NHL. Given its advantage of immediate availability, haploidentical donors should be preferably used in patients with progressive disease lacking an HLA-matched related donor. Full article
(This article belongs to the Special Issue Treatment of Peripheral T-cell Lymphomas)
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Review

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17 pages, 296 KiB  
Review
Nodal Peripheral T-Cell Lymphoma: Therapeutic Challenges and Future Perspectives
by Ho Pui Jeff Lam, Faisal Amin, Suzanne O. Arulogun and Mary Gleeson
Cancers 2025, 17(7), 1134; https://doi.org/10.3390/cancers17071134 - 28 Mar 2025
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Abstract
Peripheral T-cell lymphomas (PTCLs) present a significant clinical challenge despite recent advances in the development of novel therapeutic agents, guided by a deeper understanding of the pathobiology and the genetic and molecular characteristics underlying this complex and heterogeneous group of aggressive non-Hodgkin lymphomas [...] Read more.
Peripheral T-cell lymphomas (PTCLs) present a significant clinical challenge despite recent advances in the development of novel therapeutic agents, guided by a deeper understanding of the pathobiology and the genetic and molecular characteristics underlying this complex and heterogeneous group of aggressive non-Hodgkin lymphomas (NHLs) [...] Full article
(This article belongs to the Special Issue Treatment of Peripheral T-cell Lymphomas)
22 pages, 1968 KiB  
Review
Antibody-Based Therapies for Peripheral T-Cell Lymphoma
by Nazila Shafagati, Suman Paul, Sima Rozati and Cole H. Sterling
Cancers 2024, 16(20), 3489; https://doi.org/10.3390/cancers16203489 - 15 Oct 2024
Cited by 2 | Viewed by 2349
Abstract
While antibody-based immunotherapeutic strategies have revolutionized the treatment of B-cell lymphomas, progress in T-cell lymphomas has suffered from suboptimal targets, disease heterogeneity, and limited effective treatment options. Nonetheless, recent advances in our understanding of T-cell biology, the identification of novel targets, and the [...] Read more.
While antibody-based immunotherapeutic strategies have revolutionized the treatment of B-cell lymphomas, progress in T-cell lymphomas has suffered from suboptimal targets, disease heterogeneity, and limited effective treatment options. Nonetheless, recent advances in our understanding of T-cell biology, the identification of novel targets, and the emergence of new therapies provide hope for the future. In this review, we explore four areas of current and evolving antibody-based strategies for the treatment of peripheral T-cell lymphoma (PTCL): monoclonal antibodies (mAbs), bispecific antibodies (BsAs), chimeric antigen receptor T-cell therapy (CAR-T), and antibody–drug conjugates (ADCs). As part of this discussion, we will also include limitations, lessons learned, and potential future directions. Full article
(This article belongs to the Special Issue Treatment of Peripheral T-cell Lymphomas)
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