IL2RA expression

A significant portion of this review examines the evolving therapeutic landscape, scrutinizing Treg-depleting antibodies (e.g., mogamulizumab, RG6292), immunomodulatory small molecules (venetoclax, hypomethylating agents, TKIs), and the challenges Tregs pose to cellular therapies. Finally, we discuss novel strategies to circumvent Treg-mediated resistance, offering a perspective on restoring anti-leukemic immunity.

In addition, it was found that IL-2 significantly decreased the expression of the inhibitory receptor CTLA-4 and increased the expression of B lymphocyte-induced maturation protein-1(Blimp-1), leading to the activation of effector T cells and the induction apoptosis of the breast tumor cells. These findings suggest that IL-2 could serve as a new treatment strategy for breast cancer via modulating immune responses within the TME.

BC can be a practical and effective source of PBMCs for T cell engineering. These findings underscore the SR signaling in the activation of CD4+ T cells that may impact the activation of CD8+ T cells, which is essential for effective tumor eradication.

ISM should be considered in patients with atypical vertebral fractures, particularly when BMD is normal. Serum tryptase, KIT mutation testing, and bone biopsy enable timely diagnosis and treatment to prevent further skeletal morbidity.

A deeper understanding of Treg regulation is needed to unlock their therapeutic potential without compromising immune equilibrium.

However, after FDR correction, none of the causal associations remained statistically significant. Our research offers compelling genetic evidence supporting a forward causal link between CD39⁺ CD8⁺ T cells, CD25 on IgD- CD27- B cells, and HLA-DR on CD14⁺ CD16- monocytes and UF, and a reverse causal link between CD39⁺ CD8⁺ T cells and UF, highlighting immune regulation as a potentially pivotal factor in UF pathogenesis.

Tumor PD-L1 is associated with better PFS and OS after ipilimumab + nivolumab. In the sarcomatoid/rhabdoid subset, lower CD25 (a marker of regulatory T cells) was associated with improved PFS, while increased neutrophil infiltration (CD66b+/MPO+) emerged as a novel feature of sarcomatoid/rhabdoid tumors, which may be harnessed for therapeutic benefit in this population.

CD123 is frequently expressed on neoplastic MCs in SM by flow cytometry, across all subtypes. These findings support further investigation of CD123 as a therapeutic target and warrant correlation with IHC and clinical outcomes in larger cohorts.

Notably, the SM component was negative for KIT D816V mutation, as expected for WD-SM; however, the immunophenotype was atypical with aberrant expression of CD25. This case highlights the potential for solid tumor genomics to expose occult myeloid neoplasms incidentally and underscores the importance of a comprehensive workup, including bone marrow examination, in distinguishing between incidental clonal hematopoiesis and bona fide myeloid neoplasms.

In the present study, we investigated whether combining reduced-dose 177Lu-CD25 Ab radioimmunotherapy (RIT) with molecularly targeted inhibitors of ALK (crizotinib) or mTOR (everolimus) could enhance antitumor efficacy while minimizing systemic toxicity. These findings demonstrate that targeted inhibition of ALK or mTOR synergizes with CD25-directed 177Lu RIT to enhance therapeutic efficacy without increasing toxicity. This combinatorial approach enables radiation-dose reduction while preserving antitumor potency, supporting further preclinical and translational development of 177Lu-CD25-based combination RIT for ALCL and other CD25-expressing malignancies.

In vivo, CD25-ApDC achieved complete tumor remission in xenograft and disseminated models with optimized dosing, showing efficacy and tolerability comparable to Brentuximab vedotin. Increasing drug-to-aptamer ratios further enhanced outcomes, supporting flexible dosing strategies. These findings highlight CD25-ApDC as a promising therapeutic modality for hematologic malignancies, offering advantages in specificity, tissue penetration, and manufacturability over conventional antibody-based therapies.

Mechanistically, PD-1/IL-2 bsAb-driven STAT5 activation transcriptionally upregulates CD47 on CD8+ T cells, which shields them from macrophage-mediated phagocytosis and enhances T cell survival in the tumor microenvironment. These findings delineate a role for the IL-2-STAT5-CD47 axis in immune evasion and suggest reactivating this pathway with PD-1/IL-2 bsAb may represent a therapeutic strategy to overcome resistance in this subtype.