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The Development of Immunotherapies to Treat Lymphoma

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

Deadline for manuscript submissions: closed (31 March 2026) | Viewed by 2889

Special Issue Editor


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Guest Editor
Laboratory of Hematology, Division of Laboratory Medicine, School of Medicine, University of Crete, Heraklion, Greece
Interests: lymphomas; immune regulation

Special Issue Information

Dear Colleagues,

We are pleased to announce a call for submissions for a Special Issue of Cancers, entitled “The Development of Immunotherapies to Treat Lymphoma”. Lymphoma, a diverse group of hematologic malignancies, has seen significant therapeutic advances in recent years, particularly with the advent of immunotherapy.

This Special Issue aims to explore the latest research and clinical developments in the field of immunotherapy for lymphoma. We invite researchers to submit original articles and comprehensive reviews addressing all aspects of immunotherapeutic strategies, including, but not limited to, the following:

  1. Mechanisms of immune evasion and immune system interactions in lymphoma.
  2. Development and clinical application of monoclonal antibodies.
  3. Chimeric antigen receptor (CAR) T-cell therapies and bispecific T-cell engagers.
  4. Immune checkpoint inhibitors and their role in lymphoma treatment.
  5. Combination therapies and personalized approaches to immunotherapy.
  6. Challenges and opportunities in translating immunotherapies from bench to bedside.

All submitted manuscripts will undergo a rigorous peer-review process to ensure the highest scientific quality and relevance to the field. We welcome contributions from researchers, clinicians, and industry experts working to advance the field of lymphoma pathogenesis and treatment.

By consolidating the latest findings and innovative approaches, this Special Issue aims to deepen our understanding of lymphoma immunobiology and to promote the development of novel immunotherapies. We believe that your valuable insights will significantly contribute to the success of the Special Issue.

For any inquiries or further information, please feel free to contact us. We are committed to supporting your participation in this Special Issue.

Thank you for your attention, and we eagerly anticipate your submissions.

Dr. Christina Kalpadakis
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 250 words) can be sent to the Editorial Office for assessment.

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

  • lymphoma immunotherapy
  • CAR T-cell therapy
  • immune checkpoint inhibitors
  • monoclonal antibodies
  • personalized immunotherapy

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Published Papers (3 papers)

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Research

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19 pages, 12167 KB  
Article
Immune Correlates of Denileukin Diftitox Treatment in TFH-Type Lymphoma
by Tatsuro Jo, Takahiro Sakai, Kazuhiro Noguchi, Kaori Yamaguchi, Kaho Umemoto, Masatoshi Matsuo, Yasushi Sawayama, Jun Taguchi, Ritsuko Kubota-Koketsu, Kuniko Abe and Kazuto Shigematsu
Cancers 2026, 18(10), 1529; https://doi.org/10.3390/cancers18101529 - 9 May 2026
Viewed by 292
Abstract
Background/Objectives: Follicular helper T-cell (TFH)-type lymphomas, including angioimmunoblastic T-cell lymphoma (AITL) and TFH lymphoma, not otherwise specified (TFH-NOS), are characterized by marked immune dysregulation in the tumor microenvironment. We investigated whether TFH-type lymphomas are enriched in immunosuppressive cells and explored immunologic changes associated [...] Read more.
Background/Objectives: Follicular helper T-cell (TFH)-type lymphomas, including angioimmunoblastic T-cell lymphoma (AITL) and TFH lymphoma, not otherwise specified (TFH-NOS), are characterized by marked immune dysregulation in the tumor microenvironment. We investigated whether TFH-type lymphomas are enriched in immunosuppressive cells and explored immunologic changes associated with denileukin diftitox (DD) treatment. Methods: FOXP3-positive mononuclear cells were quantified by immunohistochemistry in lymph node specimens from 10 patients with TFH-type lymphoma and six with non-TFH-type T-cell lymphoma. Paired skin biopsy specimens obtained before and after DD treatment from two patients with AITL were evaluated for CD4, CD8, CD68, CD163, and FOXP3 expression. Longitudinal flow cytometric T-cell receptor Vβ repertoire analysis of CD8-positive T-cell subsets was performed in three patients with AITL treated with DD. Clinical responses were retrospectively assessed in seven patients with relapsed or refractory TFH-type lymphoma treated with DD. Results: TFH-type lymphomas showed significantly higher intra-tumoral FOXP3-positive cell densities than non-TFH-type lymphomas (p = 0.0024). In paired skin biopsies, DD treatment was associated with reductions in CD68- and CD163-positive macrophage-rich infiltrates and a suggested decrease in FOXP3-positive cells. Among seven patients treated with DD, the overall response rate was 86%, including one complete response and five partial responses. Responders showed selective Vβ over-representation patterns in effector and/or memory CD8-positive T-cell subsets, whereas such findings were not convincing in the non-responder. Conclusions: TFH-type lymphomas were associated with higher FOXP3-positive cell density than selected non-TFH-type comparators. DD treatment may be associated with changes in tissue immune infiltrates and peripheral CD8/TCR Vβ skewing in responding cases, although these findings remain exploratory and do not establish causality. Full article
(This article belongs to the Special Issue The Development of Immunotherapies to Treat Lymphoma)
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11 pages, 587 KB  
Article
Real World Outcomes of Patients with Aggressive Lymphoma and Autoimmune Disease Treated with CART
by Nicole J. Altomare, Megan M. Herr, Nisha M. Nair, Deborah M. Stephens, Jonathon B. Cohen, Narendranath Epperla, Matthew Cortese, Rahul Bhansali, Tamara K. Moyo, Vaishalee Kenkre, Thomas Ollila, Brian Hess, Lindsey Fitzgerald, Geoffrey Shouse, James A. Davis, Christy Jesme, Ari Pelcovits, Jonathan Moreira, Adam Lin, Shuo Ma, Jane N. Winter, Alexey Danilov, Stefan K. Barta, Leo I. Gordon, Jason Romancik, Natalie S. Grover and Reem Karmaliadd Show full author list remove Hide full author list
Cancers 2025, 17(14), 2358; https://doi.org/10.3390/cancers17142358 - 16 Jul 2025
Viewed by 1663
Abstract
Autoimmune diseases (AIDs) have been shown to be a risk factor for the development of non-Hodgkin lymphoma (NHL), with more than 15 million Americans diagnosed with AIDs between 2011 and 2022 [...] Full article
(This article belongs to the Special Issue The Development of Immunotherapies to Treat Lymphoma)
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Review

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42 pages, 1026 KB  
Review
Immunotherapy in NK/T-Cell Lymphoma: Mechanisms, Clinical Evidence, Resistance, and Emerging Multimodal Strategies
by Qihao Zhang and Xin Wang
Cancers 2026, 18(9), 1358; https://doi.org/10.3390/cancers18091358 - 24 Apr 2026
Viewed by 461
Abstract
Natural killer/T-cell lymphoma (NKTCL) is a rare and aggressive Epstein–Barr virus (EBV)-associated lymphoma characterized by intrinsic chemoresistance and an immunosuppressive tumor immune microenvironment (TIME). EBV-driven immune dysregulation provides a biological rationale for immunotherapy. This review summarizes current advances in immunotherapeutic strategies for NKTCL, [...] Read more.
Natural killer/T-cell lymphoma (NKTCL) is a rare and aggressive Epstein–Barr virus (EBV)-associated lymphoma characterized by intrinsic chemoresistance and an immunosuppressive tumor immune microenvironment (TIME). EBV-driven immune dysregulation provides a biological rationale for immunotherapy. This review summarizes current advances in immunotherapeutic strategies for NKTCL, integrating molecular mechanisms, clinical evidence, and resistance mechanisms within the context of TIME remodeling and immune reprogramming. We synthesize evidence from clinical trials, translational studies, and preclinical investigations evaluating immune checkpoint inhibitors, antibody-based therapies, adoptive cellular therapies, immune engagers, EBV-directed immunotherapies, and multimodal combination strategies in NKTCL. Among these strategies, PD-1/PD-L1 inhibitors are the most extensively studied immunotherapies in NKTCL and demonstrate clinically meaningful activity across different clinical settings. However, therapeutic responses remain heterogeneous, and primary or acquired resistance is common, driven by EBV-associated immune suppression, defective antigen presentation, metabolic reprogramming, and multi-checkpoint co-expression. Beyond immune checkpoint blockade, emerging approaches—including dual-checkpoint inhibition, epigenetic and metabolic combinations, antibody–drug conjugates, EBV-specific cytotoxic T lymphocytes, chimeric antigen receptor (CAR)-based platforms, immune engagers, and EBV vaccines—have shown encouraging signals in early-phase studies. Increasing evidence also supports multimodal strategies integrating immunotherapy with radiotherapy and other immune-modulatory interventions to enhance immune reprogramming and improve response durability. Overall, immunotherapy has substantially expanded the therapeutic landscape of NKTCL but remains constrained by complex EBV–TIME interactions and interpatient heterogeneity. Future progress will rely on biologically informed patient stratification, rational multimodal combination strategies, and integration of innovative immune platforms to establish a durable, immune-reprogramming-centered treatment paradigm for EBV-driven NKTCL. Full article
(This article belongs to the Special Issue The Development of Immunotherapies to Treat Lymphoma)
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