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Study on the Microenvironment in Lymphoma
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Study on the Microenvironment in Lymphoma

A special issue of International Journal of Molecular Sciences (ISSN 1422-0067). This special issue belongs to the section "Molecular Oncology".

Deadline for manuscript submissions: 20 February 2026 | Viewed by 1792

Special Issue Editor

Dr. Jonathan P. Butchar

E-Mail Website
Guest Editor
Department of Internal Medicine, Division of Hematology, The Ohio State University, Columbus, OH 43210, USA
Interests: leukemia, lymphocytic, chronic, B-cell; tularemia; neoplasms; infection
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

We are excited to create this Special Issue dedicated to the Study of the Microenvironment in Lymphoma. Numerous types of lymphoma have been identified, and for each there are critical interactions that take place between tumor cells and the cells and structures within their immediate surroundings. Direct cell-to-cell communication as well as signaling via secreted factors such as cytokines and exosomes play a role in promoting tumor-cell survival and proliferation. Here in this Special Issue we wish to explore novel discoveries and recent advances related to the lymphoma microenvironment. This will help expand our understanding of lymphoma and may ultimately lead to novel therapies. Original research and reviews of the latest discoveries would both be welcome within this Issue.

Dr. Jonathan P. Butchar
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 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. 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

  • tumor microenvironment
  • lymphoma
  • hodgkin lymphoma
  • non-hodgkin lymphoma
  • burkitt lymphoma
  • follicular lymphoma
  • waldenström’s macroglobulinemia
  • NK/T-cell lymphoma
  • diffuse large B-cell lymphoma
  • mantle cell lymphoma
  • marginal zone lymphoma
  • lymphoproliferative disorder
  • anaplastic large cell lymphoma
  • mediastinal B cell lymphoma
  • T-cell lymphomas

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Published Papers (2 papers)

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Research

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10 pages, 2295 KB  
Communication
CD5 Expression in CTCL and Its Implications for Anti-CD5 CAR T-Cell Therapy
by Leena Wardeh, Madeline Williams, Courtney Prestwood, Zachary Wolner and Neda Nikbakht
Int. J. Mol. Sci. 2025, 26(21), 10411; https://doi.org/10.3390/ijms262110411 - 27 Oct 2025
Viewed by 652
Abstract
Cutaneous T-Cell Lymphomas (CTCL) are a heterogenous group of T-cell malignancies in the skin and have poor treatment outcomes in advanced stages. CD5, a surface glycoprotein expressed on most mature T cells, has emerged as a promising target for chimeric antigen receptor (CAR) [...] Read more.
Cutaneous T-Cell Lymphomas (CTCL) are a heterogenous group of T-cell malignancies in the skin and have poor treatment outcomes in advanced stages. CD5, a surface glycoprotein expressed on most mature T cells, has emerged as a promising target for chimeric antigen receptor (CAR) T-cell therapy in systemic T-cell lymphomas. However, its expression profile in CTCL and relevance for targeted therapy remain unclear. Notably, in CTCL, the cell surface expression of receptors, such as CD7 and CD26, tends to become downregulated on the surfaces of malignant T cells In this study, we analyzed single-cell RNA sequencing (scRNA-seq) data from patients at two institutions with mycosis fungoides (MF), the most common subtype of CTCL with a predominantly CD4 phenotype. We utilized 5 patch/plaque MF skin biopsies (majority from early-stage patients), 8 MF tumor biopsies (all from advanced-stage patients), and 8 healthy control biopsies to evaluate lesion-specific CD5 gene expression on CD4 T cells. We found that CD5 was significantly increased in malignant MF CD4 T cells compared to healthy control CD4 T cells (21.1% of MF CD4 T cells expressed CD5 vs. 5.2% of healthy control CD4 T cells, respectively). In subgroup analysis, patch/plaque stage MF biopsies showed higher expression of CD5 in CD4 T cells than tumor stage MF biopsies. Notably, 94.3% of malignant CD4+ T cells in tumor stage MF lesions exhibited complete CD5 loss compared to only 76.6% in patch-plaque MF lesions, suggesting antigen escape in tumor stage disease. These findings demonstrate that CD5 expression in CTCL is dynamic and varies based on lesion type. Our work suggests CD5 may be a viable therapeutic target in MF with patch/plaque presentations but may not be as effective in advanced stages of MF with tumor presentations. This work informs CD5 gene expression in MF based on clinical lesion type and further information is needed to clarify clinical implications as a future therapeutic target. Full article
(This article belongs to the Special Issue Study on the Microenvironment in Lymphoma)
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Review

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32 pages, 812 KB  
Review
The Significance of the Microenvironment in T/Nk-Cell Neoplasms
by Ivan Petković, Michele Ritucci, Ana Stojković, Slavica Stojnev, Aleksandar Popović, Irena Conić, Milica Radić, Miljana Džunić and Miljan Krstić
Int. J. Mol. Sci. 2025, 26(22), 11225; https://doi.org/10.3390/ijms262211225 - 20 Nov 2025
Viewed by 851
Abstract
T/NK-cell neoplasms represent rare and highly diverse cancers, distinguished by variability in their molecular architecture, local inflammatory milieu, and microenvironmental composition, which collectively underpin the diversity of clinical presentations and outcomes. The neoplastic tissue comprises malignant lymphoma/leukemic cells in concert with a spectrum [...] Read more.
T/NK-cell neoplasms represent rare and highly diverse cancers, distinguished by variability in their molecular architecture, local inflammatory milieu, and microenvironmental composition, which collectively underpin the diversity of clinical presentations and outcomes. The neoplastic tissue comprises malignant lymphoma/leukemic cells in concert with a spectrum of stromal elements and the acellular extracellular matrix (ECM), collectively constituting the lymphoma microenvironment (LME). These components engage in dynamic, reciprocal interactions, forming a self-regulating ecosystem capable of responding adaptively to both exogenous and endogenous stimuli. Historically, the LME was largely neglected in considerations of lymphomagenesis; however, emerging evidence highlights its pivotal role in driving core oncogenic processes, including sustained proliferative signaling, angiogenesis, immune evasion, and apoptotic resistance. Deciphering the intricate, multidirectional crosstalk among the cellular and acellular constituents of the T/NK-cell neoplastic microenvironment promises to deepen our understanding of disease biology and may inform the development of novel, mechanism-based therapeutic interventions. Full article
(This article belongs to the Special Issue Study on the Microenvironment in Lymphoma)
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