IL2RA expression

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.

Four injections of a CD25 antibody-drug conjugate induced complete remission in mice transplanted with PDX refractory leukemia. These findings highlight the dependency of tyrosine kinase-driven leukemias on robust feedback control and the role of PKCδ and CD25 in assembling its components.

In addition, CD25 on resting regulatory T cell (Treg) was negatively correlated with LUAD. Of note, the mediation MR illustrated that in the presence of CD25 on resting Treg, PWY-5989 can promote the risk of LUAD by inhibiting the expression of CD25 on resting Treg. The study suggested a causal relationship between PWY-5989 and LUAD, which may be mediated by CD25 on resting Treg.

In multivariate analysis, higher PB blast percentage, CD25 positivity, and ECOG PS ≥ 2 independently predicted poorer OS. Although LA did not reduce early mortality in the entire cohort, the loss of prognostic significance of elevated LDH, high PB blast percentage, PB monocyte burden, and CD25 expression in the LA group may suggest that the intervention can attenuate the impact of biologically aggressive disease.

In addition, combined treatment with BPA and 5-fluorouracil (5-FU), a commonly used chemotherapeutic agent for CRC, notably enhanced the anti-tumor effect in mice. These findings indicate that BPA, an active extract of B. pilosa L., showed antitumor activity in mice by suppressing the differentiation of pro-tumorigenic TAMs and Tregs within the TME.

AML with KMT2A-PTD shows distinctive immunophenotypic features with increased CD123 and aberrant CD25 expression, both associated with FLT3-ITD. These markers may have diagnostic and therapeutic relevance in this AML subtype.

Overall, the IL-12 release substantially improved effector functionality against CD176+ cells but not CD176- cells, indicating efficacy while maintaining specificity. Thus, CD176-iIL12-TRUCKs, with their potent antitumor efficacy and TME modulation potential, are a promising treatment option for patients with a variety of advanced solid tumors.

In orthotopic tumor models, mimicking systemic loss of Il27ra significantly reduced tumor growth and prolonged survival in immunocompetent mice, with single-cell profiling indicating enhanced intratumoral T-cell and NK-cell effector activity. Collectively, our findings identify an epithelial-intrinsic IL27RA-PI3K/AKT-MHC-I axis as a central driver of immune evasion and ICB resistance in TNBC and support IL27RA as a promising therapeutic target for overcoming immunotherapy resistance.

In summary, exosomal PA28γ induces a T-cell exhaustion phenotype by inhibiting their tumor-killing ability, promoting malignant progression via the PA28γ/BCLAF1/CD25&LAG-3 pathway. These findings reveal a novel cell‒cell interaction between tumors and T cells in the HNSCC microenvironment.

This activation was specifically abolished by ICOSL blockade, establishing the functional significance of this pathway. Our findings provide novel insights into tumor-immune interactions in cholangiocarcinoma and suggest the ICOS-ICOSL axis as a potential therapeutic target for immunotherapy.