Clinicopathological significance of CD28 overexpression in adult T‐cell leukemia/lymphoma

Sakamoto, Yuma; Ishida, Takashi; Awata, Masaki; Takeshita, Morishige; Iwasaki, Hiromi; Yonekura, Kentaro; Tashiro, Yoshihiko; Ito, Asahi; Kusumoto, Shigeru; Iida, Shinsuke; Utsunomiya, Atae; Ueda, Ryuzo; Inagaki, Hiroshi

doi:10.1111/cas.15191

Cited by 8 publications

(2 citation statements)

References 45 publications

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“…Due to its role in malignant lymphocyte chemotaxis, CCR4 is expressed in MF (including CD8 + subtypes), SS, and other lymphomas [ 46 ], such as T-cell leukaemia/lymphoma (ATLL) [ 47 ].…”

Section: The Ccr4 Receptormentioning

confidence: 99%

“…Compound [ 8 , 9 , 10 , 11 , 12 , 13 , 14 , 15 , 16 , 17 , 18 , 19 , 20 , 21 , 22 , 23 , 24 , 25 , 26 , 27 , 28 , 29 , 30 , 31 , 32 , 33 , 34 , 35 , 36 , 37 , 38 , 39 , 40 , 41 , 42 , 43 , 44 , 45 , 46 , 47 , 48 , 49 , 50 , 51 , 52 , 53 , 54 , 55 , 56 , 57 , 58 , 59 , 60 , …”

Section: The Developed and Under-investigation Treatments To Address ...unclassified

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A Narrative Review of the State of the Art of CCR4-Based Therapies in Cutaneous T-Cell Lymphomas: Focus on Mogamulizumab and Future Treatments

Zengarini,

Guglielmo,

Mussi

et al. 2024

Antibodies

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The CCR4 receptor is a pivotal target in cutaneous T-cell lymphoma (CTCL) therapy due to its role in impairing immune responses against malignant T-cells and expression profiles. Monoclonal antibodies like mogamulizumab effectively bind to CCR4, reducing tumour burden and enhancing patient outcomes by inhibiting the receptor’s interaction with ligands, thereby hindering malignant T-cell migration and survival. Combining CCR4 antibodies with chemotherapy, radiation, and other drugs is being explored for synergistic effects. Additionally, small-molecular inhibitors, old pharmacological agents interacting with CCR4, and CAR-T therapies are under investigation. Challenges include drug resistance, off-target effects, and patient selection, addressed through ongoing trials refining protocols and identifying biomarkers. Despite advancements, real-life data for most of the emerging treatments are needed to temper expectations. In conclusion, CCR4-targeted therapies show promise for CTCL management, but challenges persist. Continued research aims to optimise treatments, enhance outcomes, and transform CTCL management. This review aims to elucidate the biological rationale and the several agents under various stages of development and clinical evaluation with the actual known data.

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“…Due to its role in malignant lymphocyte chemotaxis, CCR4 is expressed in MF (including CD8 + subtypes), SS, and other lymphomas [ 46 ], such as T-cell leukaemia/lymphoma (ATLL) [ 47 ].…”

Section: The Ccr4 Receptormentioning

confidence: 99%

Section: The Developed and Under-investigation Treatments To Address ...unclassified

A Narrative Review of the State of the Art of CCR4-Based Therapies in Cutaneous T-Cell Lymphomas: Focus on Mogamulizumab and Future Treatments

Zengarini,

Guglielmo,

Mussi

et al. 2024

Antibodies

View full text Add to dashboard Cite

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Treatment of Adult T-Cell Leukemia/Lymphoma: Established Paradigms and Emerging Directions

Stuver

Horwitz

Epstein‐Peterson

2023

Curr. Treat. Options in Oncol.

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BACH2-mediated CD28 and CD40LG axes contribute to pathogenesis and progression of T-cell lymphoblastic leukemia

Feng,

Zhang,

et al. 2024

Cell Death Dis

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T-cell acute lymphoblastic leukemia (T-ALL) is an aggressive subtype of ALL characterized by its high heterogeneity and unfavorable clinical features. Despite improved insights in genetic and epigenetic landscapes of T-ALL, the molecular mechanisms that drive malignant T-cell development remain unclear. BTB and CNC homology 2 (BACH2) is a lymphoid-specific transcription repressor recognized as a tumor suppressor in B-cell malignancies, but little is known about its function and regulatory network in T-ALL. Here we found extremely low levels of BACH2 in T-ALL clinical samples and cell lines compared to normal T cells. Overexpression of BACH2 in T-ALL cells not only induced cell growth retardation but also inhibited cancer progression and infiltration in xenografts. Further RNA sequencing (RNA-seq) analysis revealed significant alterations in regulation of defense and immune responses in T-ALL cells upon BACH2 overexpression. Strikingly, CD28 and CD40LG, two essential stimulatory molecules on T cells, were for the first time identified as novel downstream targets repressed by BACH2 in T-ALL cells. Interestingly, both CD28 and CD40LG were indispensable for T-ALL survival, since largely or completely silencing CD28 and CD40LG led to rapid cell death, whereas partial knockdown of them resulted in cell-cycle arrest and enhanced apoptosis. More importantly, BACH2-mediated CD28 and CD40LG signals contributed to cell migration and dissemination of T-ALL cells to the bone marrow, thus adding a new layer to the BACH2-mediated tumor immunoregulation in T-cell malignancies.

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Clinicopathological significance of CD28 overexpression in adult T‐cell leukemia/lymphoma

Abstract: This is an open access article under the terms of the Creat ive Commo ns Attri butio n-NonCo mmerc ial-NoDerivs License, which permits use and distribution in any medium, provided the original work is properly cited, the use is non-commercial and no modifications or adaptations are made.

Cited by 8 publications

References 45 publications

A Narrative Review of the State of the Art of CCR4-Based Therapies in Cutaneous T-Cell Lymphomas: Focus on Mogamulizumab and Future Treatments

A Narrative Review of the State of the Art of CCR4-Based Therapies in Cutaneous T-Cell Lymphomas: Focus on Mogamulizumab and Future Treatments

Treatment of Adult T-Cell Leukemia/Lymphoma: Established Paradigms and Emerging Directions

BACH2-mediated CD28 and CD40LG axes contribute to pathogenesis and progression of T-cell lymphoblastic leukemia

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