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Cancers
Special Issues
Novel Targeted Therapies for T-cell Malignancies
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Novel Targeted Therapies for T-cell Malignancies

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

Deadline for manuscript submissions: 30 November 2024 | Viewed by 11453

Special Issue Editor

Dr. Melania Tesio

E-Mail Website
Guest Editor
UR LIB "Lymphoma Immune biology", University Claude Bernard Lyon I, 69376 Lyon, France
Interests: T-cell neoplasms; leukemia-initiating cells; molecular targets

Special Issue Information

Dear Colleagues,

T-cell malignancies are a broad range of disorders characterized by the clonal proliferation of T cells arrested at different developmental stages. This heterogeneous group of diseases presents with distinct clinical behavior and overall prognosis. Overall, however, only a limited number of therapeutic strategies are effective for patients presenting with T-cell leukemias or lymphomas, especially following relapse. In recent years, the molecular and genomic characterization of these disorders has contributed to identify novel therapeutic targets, leading to the development of novel target therapies including small molecule inhibitors, antibodies-based treatment, and cellular therapies.

We are pleased to invite you to join this Special Issue of Cancers which aims at providing an up-to-date perspective over distinct targeted therapies against T-cell neoplasms, including T-ALL, T-cell lymphomas, and T-cell lymphoblastic lymphomas.

In this Special Issue, original research articles, translational, clinical trials, and reviews are welcome. Research areas may include (but are not limited to) the following:

  • CAR T-cells;
  • Immune checkpoint inhibitors;
  • Bi-specific antibodies;
  • Monoclonal antibodies;
  • Small molecules inhibitors;
  • Molecular and cellular targets;
  • Novel animal models for drug testing and developing immune and cellular-based therapies.

Dr. Melania Tesio
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

  • CAR T cells
  • immune checkpoints
  • bi-specific antibodies
  • T-cell leukemia
  • T-cell lymphomas
  • T-LBL
  • immunotherapy
  • cellular therapies

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Further information on MDPI's Special Issue polices can be found here.

Published Papers (6 papers)

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Editorial

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4 pages, 208 KiB  
Editorial
Novel Targeted Therapies for T-Cell Malignancies
by Melania Tesio
Cancers 2022, 14(16), 3955; https://doi.org/10.3390/cancers14163955 - 16 Aug 2022
Viewed by 1461
Abstract
T-cell malignancies comprise a heterogeneous group of cancers resulting from the clonal expansion of T-cells at different developmental stages [...] Full article
(This article belongs to the Special Issue Novel Targeted Therapies for T-cell Malignancies)

Research

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17 pages, 3197 KiB  
Article
A Combination of Alectinib and DNA-Demethylating Agents Synergistically Inhibits Anaplastic-Lymphoma-Kinase-Positive Anaplastic Large-Cell Lymphoma Cell Proliferation
by Kazunori Kawasoe, Tatsuro Watanabe, Nao Yoshida-Sakai, Yuta Yamamoto, Yuki Kurahashi, Keisuke Kidoguchi, Hiroshi Ureshino, Kazuharu Kamachi, Yuki Fukuda-Kurahashi and Shinya Kimura
Cancers 2023, 15(20), 5089; https://doi.org/10.3390/cancers15205089 - 21 Oct 2023
Viewed by 1839
Abstract
The recent evolution of molecular targeted therapy has improved clinical outcomes in several human malignancies. The translocation of anaplastic lymphoma kinase (ALK) was originally identified in anaplastic large-cell lymphoma (ALCL) and subsequently in non-small cell lung carcinoma (NSCLC). Since ALK fusion gene products [...] Read more.
The recent evolution of molecular targeted therapy has improved clinical outcomes in several human malignancies. The translocation of anaplastic lymphoma kinase (ALK) was originally identified in anaplastic large-cell lymphoma (ALCL) and subsequently in non-small cell lung carcinoma (NSCLC). Since ALK fusion gene products act as a driver of carcinogenesis in both ALCL and NSCLC, several ALK tyrosine kinase inhibitors (TKIs) have been developed. Crizotinib and alectinib are first- and second-generation ALK TKIs, respectively, approved for the treatment of ALK-positive ALCL (ALK+ ALCL) and ALK+ NSCLC. Although most ALK+ NSCLC patients respond to crizotinib and alectinib, they generally relapse after several years of treatment. We previously found that DNA-demethylating agents enhanced the efficacy of ABL TKIs in chronic myeloid leukemia cells. Moreover, aberrant DNA methylation has also been observed in ALCL cells. Thus, to improve the clinical outcomes of ALK+ ALCL therapy, we investigated the synergistic efficacy of the combination of alectinib and the DNA-demethylating agent azacytidine, decitabine, or OR-2100 (an orally bioavailable decitabine derivative). As expected, the combination of alectinib and DNA-demethylating agents synergistically suppressed ALK+ ALCL cell proliferation, concomitant with DNA hypomethylation and a reduction in STAT3 (a downstream target of ALK fusion proteins) phosphorylation. The combination of alectinib and OR-2100 markedly altered gene expression in ALCL cells, including that of genes implicated in apoptotic signaling, which possibly contributed to the synergistic anti-ALCL effects of this drug combination. Therefore, alectinib and OR-2100 combination therapy has the potential to improve the outcomes of patients with ALK+ ALCL. Full article
(This article belongs to the Special Issue Novel Targeted Therapies for T-cell Malignancies)
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19 pages, 3469 KiB  
Article
The miR-141/200c-STAT4 Axis Contributes to Leukemogenesis by Enhancing Cell Proliferation in T-PLL
by Moritz Otte, Johanna Stachelscheid, Markus Glaß, Linus Wahnschaffe, Qu Jiang, Waseem Lone, Aleksandr Ianevski, Tero Aittokallio, Javeed Iqbal, Michael Hallek, Stefan Hüttelmaier, Alexandra Schrader, Till Braun and Marco Herling
Cancers 2023, 15(9), 2527; https://doi.org/10.3390/cancers15092527 - 28 Apr 2023
Cited by 5 | Viewed by 1898
Abstract
T-prolymphocytic leukemia (T-PLL) is a rare and mature T-cell malignancy with characteristic chemotherapy-refractory behavior and a poor prognosis. Molecular concepts of disease development have been restricted to protein-coding genes. Recent global microRNA (miR) expression profiles revealed miR-141-3p and miR-200c-3p (miR-141/200c) as two of [...] Read more.
T-prolymphocytic leukemia (T-PLL) is a rare and mature T-cell malignancy with characteristic chemotherapy-refractory behavior and a poor prognosis. Molecular concepts of disease development have been restricted to protein-coding genes. Recent global microRNA (miR) expression profiles revealed miR-141-3p and miR-200c-3p (miR-141/200c) as two of the highest differentially expressed miRs in T-PLL cells versus healthy donor-derived T cells. Furthermore, miR-141/200c expression separates T-PLL cases into two subgroups with high and low expression, respectively. Evaluating the potential pro-oncogenic function of miR-141/200c deregulation, we discovered accelerated proliferation and reduced stress-induced cell death induction upon stable miR-141/200c overexpression in mature T-cell leukemia/lymphoma lines. We further characterized a miR-141/200c-specific transcriptome involving the altered expression of genes associated with enhanced cell cycle transition, impaired DNA damage responses, and augmented survival signaling pathways. Among those genes, we identified STAT4 as a potential miR-141/200c target. Low STAT4 expression (in the absence of miR-141/200c upregulation) was associated with an immature phenotype of primary T-PLL cells as well as with a shortened overall survival of T-PLL patients. Overall, we demonstrate an aberrant miR-141/200c-STAT4 axis, showing for the first time the potential pathogenetic implications of a miR cluster, as well as of STAT4, in the leukemogenesis of this orphan disease. Full article
(This article belongs to the Special Issue Novel Targeted Therapies for T-cell Malignancies)
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Review

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20 pages, 908 KiB  
Review
Histone Deacetylase Inhibitors for Peripheral T-Cell Lymphomas
by Ruxandra Irimia and Pier Paolo Piccaluga
Cancers 2024, 16(19), 3359; https://doi.org/10.3390/cancers16193359 - 30 Sep 2024
Viewed by 575
Abstract
Histone deacetylase inhibitors (HDACis) are being recognized as a potentially effective treatment approach for peripheral T-cell lymphomas (PTCLs), a heterogeneous group of aggressive malignancies with an unfavorable prognosis. Recent evidence has shown that HDACis are effective in treating PTCL, especially in cases where [...] Read more.
Histone deacetylase inhibitors (HDACis) are being recognized as a potentially effective treatment approach for peripheral T-cell lymphomas (PTCLs), a heterogeneous group of aggressive malignancies with an unfavorable prognosis. Recent evidence has shown that HDACis are effective in treating PTCL, especially in cases where the disease has relapsed or is resistant to conventional treatments. Several clinical trials have demonstrated that HDACis, such as romidepsin and belinostat, can elicit long-lasting positive outcomes in individuals with PTCLs, either when used alone or in conjunction with conventional chemotherapy. They exert their anti-tumor effects by regulating gene expression through the inhibition of histone deacetylases, which leads to cell cycle arrest, induction of programmed cell death, and,the transformation of cancerous T cells, as demonstrated by gene expression profile studies. Importantly, besides clinical trials, real-world evidence indicated that the utilization of HDACis presents a significant and beneficial treatment choice for PTCLs. However, although HDACis showed potential effectiveness, they could not cure most patients. Therefore, new combinations with conventional drugs as well as new targeted agents are under investigation. Full article
(This article belongs to the Special Issue Novel Targeted Therapies for T-cell Malignancies)
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Graphical abstract

30 pages, 1406 KiB  
Review
Education and Empowering Special Forces to Eradicate Secret Defectors: Immune System-Based Treatment Approaches for Mature T- and NK-Cell Malignancies
by Till Braun and Alexandra Schrader
Cancers 2023, 15(9), 2532; https://doi.org/10.3390/cancers15092532 - 28 Apr 2023
Cited by 1 | Viewed by 2348
Abstract
Mature T- and NK-cell leukemia/lymphoma (MTCL/L) constitute a heterogeneous group of, currently, 30 distinct neoplastic entities that are overall rare, and all present with a challenging molecular markup. Thus, so far, the use of first-line cancer treatment modalities, including chemotherapies, achieve only limited [...] Read more.
Mature T- and NK-cell leukemia/lymphoma (MTCL/L) constitute a heterogeneous group of, currently, 30 distinct neoplastic entities that are overall rare, and all present with a challenging molecular markup. Thus, so far, the use of first-line cancer treatment modalities, including chemotherapies, achieve only limited clinical responses associated with discouraging prognoses. Recently, cancer immunotherapy has evolved rapidly, allowing us to help patients with, e.g., solid tumors and also relapsed/refractory B-cell malignancies to achieve durable clinical responses. In this review, we systematically unveiled the distinct immunotherapeutic approaches available, emphasizing the special impediments faced when trying to employ immune system defense mechanisms to target ‘one of their own—gone mad’. We summarized the preclinical and clinical efforts made to employ the various platforms of cancer immunotherapies including antibody-drug conjugates, monoclonal as well as bispecific antibodies, immune-checkpoint blockades, and CAR T cell therapies. We emphasized the challenges to, but also the goals of, what needs to be done to achieve similar successes as seen for B-cell entities. Full article
(This article belongs to the Special Issue Novel Targeted Therapies for T-cell Malignancies)
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25 pages, 3320 KiB  
Review
Targeting Leukemia-Initiating Cells and Leukemic Niches: The Next Therapy Station for T-Cell Acute Lymphoblastic Leukemia?
by Ziting Zhang, Kun Yang and Han Zhang
Cancers 2022, 14(22), 5655; https://doi.org/10.3390/cancers14225655 - 17 Nov 2022
Cited by 2 | Viewed by 2414
Abstract
T-cell acute lymphoblastic leukemia (T-ALL) is an aggressive subtype of hematological malignancy characterized by its high heterogeneity and potentially life-threatening clinical features. Despite the advances in risk stratification and therapeutic management of T-ALL, patients often suffer from treatment failure and chemotherapy-induced toxicity, calling [...] Read more.
T-cell acute lymphoblastic leukemia (T-ALL) is an aggressive subtype of hematological malignancy characterized by its high heterogeneity and potentially life-threatening clinical features. Despite the advances in risk stratification and therapeutic management of T-ALL, patients often suffer from treatment failure and chemotherapy-induced toxicity, calling for greater efforts to improve therapeutic efficacy and safety in the treatment of T-ALL. During the past decades, increasing evidence has shown the indispensable effects of leukemia-initiating cells (LICs) and leukemic niches on T-ALL initiation and progression. These milestones greatly facilitate precision medicine by interfering with the pathways that are associated with LICs and leukemic niches or by targeting themselves directly. Most of these novel agents, either alone or in combination with conventional chemotherapy, have shown promising preclinical results, facilitating them to be further evaluated under clinical trials. In this review, we summarize the latest discoveries in LICs and leukemic niches in terms of T-ALL, with a particular highlight on the current precision medicine. The challenges and future prospects are also discussed. Full article
(This article belongs to the Special Issue Novel Targeted Therapies for T-cell Malignancies)
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