Challenging Cutaneous T-Cell Lymphoma: What Animal Models Tell us So Far

Bresin, Antonella; Caprini, Elisabetta; Russo, Giandomenico; Narducci, Maria Grazia

doi:10.1016/j.jid.2021.12.007

Cited by 5 publications

(5 citation statements)

References 116 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Such evidence in the literature has left the door open to the need for a clear-cut algorithm for patients eligible for biologic therapies. The restoration from a Th2 to a Th1 pattern is also one of the significant goals of the newly available drugs such as Mogamulizumab, Brentuximab Vedotin, and Chlormetine and molecules currently under clinical trial such as Pi3K inhibitors [5,127,[290][291][292][293]. From the present paper reviewing the literature, it has emerged that cytokines can be a reliable marker of some tumorigenic pathway activity, such as JAK/STAT MAPK, and the suppression of those tumorigenic pathways may be monitored by analyzing cytokine composition changes in patients.…”

Section: Discussionmentioning

confidence: 99%

The Role of Cytokines in Cutaneous T Cell Lymphoma: A Focus on the State of the Art and Possible Therapeutic Targets

Guglielmo,

Zengarini,

Agostinelli

et al. 2024

Cells

View full text Add to dashboard Cite

Cutaneous T cell lymphomas (CTCLs), encompassing mycosis fungoides (MF) and Sézary syndrome (SS), present a complex landscape influenced by cytokines and cellular responses. In this work, the intricate relationship between these inflammatory proteins and disease pathogenesis is examined, focusing on what is known at the clinical and therapeutic levels regarding the most well-known inflammatory mediators. An in-depth look is given to their possible alterations caused by novel immunomodulatory drugs and how they may alter disease progression. From this narrative review of the actual scientific landscape, Interferon-gamma (IFN-γ) emerges as a central player, demonstrating a dual role in both promoting and inhibiting cancer immunity, but the work navigates through all the major interleukins known in inflammatory environments. Immunotherapeutic perspectives are elucidated, highlighting the crucial role of the cutaneous microenvironment in shaping dysfunctional cell trafficking, antitumor immunity, and angiogenesis in MF, showcasing advancements in understanding and targeting the immune phenotype in CTCL. In summary, this manuscript aims to comprehensively explore the multifaceted aspects of CTCL, from the immunopathogenesis and cytokine dynamics centred around TNF-α and IFN-γ to evolving therapeutic modalities. Including all the major known and studied cytokines in this analysis broadens our understanding of the intricate interplay influencing CTCL, paving the way for improved management of this complex lymphoma.

show abstract

Section: Discussionmentioning

confidence: 99%

The Role of Cytokines in Cutaneous T Cell Lymphoma: A Focus on the State of the Art and Possible Therapeutic Targets

Guglielmo,

Zengarini,

Agostinelli

et al. 2024

Cells

View full text Add to dashboard Cite

show abstract

“…Recent advancements in CTCL research have led to the creation of ‘autochthonous mouse models’, effectively replicating the disease’s initial skin-based progression ( Bresin et al, 2022 ). These models, designed to modify genes in skin-homing CD4 + T cells along with localized inflammation, closely emulate CTCL’s natural development ( Luo et al, 2023 ).…”

Section: The Next Top Mouse Models: Genetically Engineered Mouse Mode...mentioning

confidence: 99%

“…4 The next top mouse models: Genetically engineered mouse models (GEMMs) advancing CTCL research by targeting skin-homing CD4 + T Cells in combination with inflammation Recent advancements in CTCL research have led to the creation of 'autochthonous mouse models', effectively replicating the disease's initial skin-based progression (Bresin et al, 2022). These models, designed to modify genes in skin-homing CD4 + T cells along with localized inflammation, closely emulate CTCL's natural development (Luo et al, 2023).…”

Section: Il-15 Overexpression Mouse Modelmentioning

confidence: 99%

“Next top” mouse models advancing CTCL research

Luo,

de Gruijl,

Vermeer

et al. 2024

Front. Cell Dev. Biol.

View full text Add to dashboard Cite

This review systematically describes the application of in vivo mouse models in studying cutaneous T-cell lymphoma (CTCL), a complex hematological neoplasm. It highlights the diverse research approaches essential for understanding CTCL’s intricate pathogenesis and evaluating potential treatments. The review categorizes various mouse models, including xenograft, syngeneic transplantation, and genetically engineered mouse models (GEMMs), emphasizing their contributions to understanding tumor-host interactions, gene functions, and studies on drug efficacy in CTCL. It acknowledges the limitations of these models, particularly in fully replicating human immune responses and early stages of CTCL. The review also highlights novel developments focusing on the potential of skin-targeted GEMMs in studying natural skin lymphoma progression and interactions with the immune system from onset. In conclusion, a balanced understanding of these models’ strengths and weaknesses are essential for accelerating the deciphering of CTCL pathogenesis and developing treatment methods. The GEMMs engineered to target specifically skin-homing CD4+ T cells can be the next top mouse models that pave the way for exploring the effects of CTCL-related genes.

show abstract

“…Interestingly, preclinical tests using different drugs on these SS cell lines confirmed the critical role of heterogeneity in the therapeutic efficacy as well, as described by Buus et al [ 58 ]. This study is of particular relevance because it may overcome the low efficiency of long-term SS cell culturing and the substantial lack of a standardized animal model to test the therapeutic efficacy in SS patients [ 84 ].…”

Section: Intratumor Heterogeneity Influences the Drug Resistance In S...mentioning

confidence: 99%

Combined High-Throughput Approaches Reveal the Signals Driven by Skin and Blood Environments and Define the Tumor Heterogeneity in Sézary Syndrome

Cristofoletti

Bresin

Fioretti

et al. 2022

Cancers

Self Cite

View full text Add to dashboard Cite

Sézary syndrome (SS) is an aggressive variant of cutaneous t-cell lymphoma characterized by the accumulation of neoplastic CD4+ lymphocytes—the SS cells—mainly in blood, lymph nodes, and skin. The tumor spread pattern of SS makes this lymphoma a unique model of disease that allows a concurrent blood and skin sampling for analysis. This review summarizes the recent studies highlighting the transcriptional programs triggered by the crosstalk between SS cells and blood–skin microenvironments. Emerging data proved that skin-derived SS cells show consistently higher activation/proliferation rates, mainly driven by T-cell receptor signaling with respect to matched blood SS cells that instead appear quiescent. Biochemical analyses also demonstrated an hyperactivation of PI3K/AKT/mTOR, a targetable pathway by multiple inhibitors currently in clinical trials, in skin SS cells compared with a paired blood counterpart. These results indicated that active and quiescent SS cells coexist in this lymphoma, and that they could be respectively treated with different therapeutics. Finally, this review underlines the more recent discoveries into the heterogeneity of circulating SS cells, highlighting a series of novel markers that could improve the diagnosis and that represent novel therapeutic targets (GPR15, PTPN13, KLRB1, and ITGB1) as well as new genetic markers (PD-1 and CD39) able to stratify SS patients for disease aggressiveness.

show abstract

Challenging Cutaneous T-Cell Lymphoma: What Animal Models Tell us So Far

Cited by 5 publications

References 116 publications

The Role of Cytokines in Cutaneous T Cell Lymphoma: A Focus on the State of the Art and Possible Therapeutic Targets

The Role of Cytokines in Cutaneous T Cell Lymphoma: A Focus on the State of the Art and Possible Therapeutic Targets

“Next top” mouse models advancing CTCL research

Combined High-Throughput Approaches Reveal the Signals Driven by Skin and Blood Environments and Define the Tumor Heterogeneity in Sézary Syndrome

Contact Info

Product

Resources

About