Regulatory T (Treg) and T helper 17 (Th17) cells play opposing roles in immune responses, and their balance critically regulates the multiple myeloma (MM) microenvironment. Despite advances in immunotherapy, current risk stratification lacks immune biomarkers.
We collected the peripheral blood and bone marrow samples from MM patients to investigate the relationships among 1q21 gain/amplification, the Treg/Th17 ratio, and MYC gene abnormalities at diagnosis, remission, and relapse. Additionally, we evaluated the prognostic impact of the Treg/Th17 ratio.
A total of 130 newly diagnosed MM patients were enrolled, with 82 patients evaluated for 1q21 gain/amplification. During remission, patients with 1q21 gain/amplification had a significantly higher Treg/Th17 ratio (1.59 vs. 0.85, P = 0.042) and MYC expression levels (70.54% vs. 32.76%, P = 0.042) compared to those without 1q21 gain/amplification. Furthermore, patients with an elevated Treg/Th17 ratio (>0.7) during remission exhibited slightly higher MYC expression (45.70% vs. 30.60%) than those with lower ratios (P = 0.451). Patients achieving partial response or better exhibited significantly higher Th17 levels (3.34%, range: 0.19-10.80%) at diagnosis compared to those without remission (0.29%, range: 0-2.18%, P = 0.033). The group of elevated Treg/Th17 ratio (> 1.0) at diagnosis exhibited significantly shorter PFS compared to the reduced ratio (≤ 1.0) group (13.87 months vs. 30.67 months, P = 0.006). R2-ISS staging showed no significant impact on PFS (P = 0.236). By assigning scores to R2-ISS stages and elevated Treg/Th17 ratio at diagnosis, patients were stratified into low-risk (1-3 scores) and high-risk (4-5 scores) groups. High-risk patients exhibited significantly worse PFS compared to low-risk patients (P = 0.022). The combined model integrating R2-ISS staging and Treg/Th17 ratio achieved a concordance index(C-index) of 0.8, surpassing the C-index of R2-ISS staging alone (0.562), demonstrating better predictive performance.
A potential mechanistic connection exists between 1q21 gain/amplification and immunosuppression, and the role of the MYC gene in this mechanism has garnered substantial interest. Patients with a higher Treg/Th17 ratio at diagnosis are more prone to relapse. The combination of R2-ISS staging and the Treg/Th17 ratio at diagnosis demonstrates stronger predictive ability for relapse.
Copyright © 2025 Wen, Zhou, Xu, Yue, Zhang, Liu, Su and Liang.

This study investigated the role of regulatory T cells (Tregs) in newly diagnosed multiple myeloma (NDMM) patients, particularly in relation to early relapse and prognosis.
The analysis included clinical data from 70 NDMM patients, with Tregs measured at diagnosis. Early relapse was defined as relapse within 18 months (ER18), and posttransplant survival extending beyond 12 months. Functional high risk (FHR) was evaluated based on this criterion.
For the overall cohort, the median progression-free survival (PFS) and overall survival (OS) were not reached, but in the ER18 cohort, median OS was 24.8 months and median PFS was 10.8 months. Key factors linked to early relapse included elevated serum creatinine levels (> 156 μmol/L), presence of extramedullary disease, and lower percentage of Tregs at diagnosis. Multivariate analysis revealed that extramedullary disease and lower percentage of Tregs were significant predictors of early relapse. Factors such as age, elevated creatinine, extramedullary disease, and lower percentage of Tregs were associated with poorer PFS. Further analysis confirmed that extramedullary lesions, elevated creatinine, and lower percentage of Tregs significantly influenced PFS.
Overall, Tregs at diagnosis were found to be important for predicting early relapse and progression-free survival, highlighting their potential as a biomarker for functional high risk in multiple myeloma.
© 2025 The Author(s). Cancer Medicine published by John Wiley & Sons Ltd.

Systemic lupus erythematosus (SLE) is an autoimmune disease with significant morbidity and mortality. Type I interferon (IFN) drives SLE pathology and plasmacytoid dendritic cells (pDCs) are potent producers of IFN; however, the specific effects of pDC depletion have not been demonstrated. We show CD123 was highly expressed on pDCs and the anti-CD123 antibody CSL362 potently depleted pDCs in vitro. CSL362 pre-treatment abrogated the induction of IFNα and IFN-induced gene transcription following stimulation with SLE patient-derived serum or immune complexes. RNA transcripts induced in pDCs by ex vivo stimulation with TLR ligands were reflected in gene expression profiles of SLE blood, and correlated with disease severity. TLR ligand-induced protein production by SLE patient peripheral mononuclear cells was abrogated by CSL362 pre-treatment including proteins over expressed in SLE patient serum. These findings implicate pDCs as key drivers in the cellular activation and production of soluble factors seen in SLE.
© 2023 The Authors.

The potential clinical application of gadolinium-neutron capture therapy (Gd-NCT) for glioblastoma multiforme (GBM) treatment has been compromised by the fast clearance and nonspecific biodistribution of gadolinium-based agents. We have developed a stem cell-nanoparticle system (SNS) to actively target GBM for advanced Gd-NCT by magnetizing umbilical cord mesenchymal stem cells (UMSCs) using gadodiamide-concealed magnetic nanoparticles (Gd-FPFNP). Nanoformulated gadodiamide shielded by a dense surface composed of fucoidan and polyvinyl alcohol demonstrates enhanced cellular association and biocompatibility in UMSCs. The SNS preserves the ability of UMSCs to actively penetrate the blood brain barrier and home to GBM and, when magnetically navigates by an external magnetic field, an 8-fold increase in tumor-to-blood ratio is achieved compared with clinical data. In an orthotopic GBM-bearing rat model, using a single dose of irradiation and an ultra-low gadolinium dose (200 μg kg-1), SNS significantly attenuates GBM progression without inducing safety issues, prolonging median survival 2.5-fold compared to free gadodiamide. The SNS is a cell-based delivery system that integrates the strengths of cell therapy and nanotechnology, which provides an alternative strategy for the treatment of brain diseases.
© 2023. The Author(s).

h4>Background: /h4> Langerhans cell histiocytosis (LCH) is an inflammatory myeloid neoplasm, immune system dysfunction may attribute to the cause of LCH. There is no standard prognosis evaluation system for LCH in children. We investigated the prognosis predictive value of peripheral lymphocyte subsets in childhood LCH patients. h4>Methods: /h4>: A cohort of 79 childhood LCH patients was retrospectively studied. The prognosis predictive significance of CD3 + T cells, CD3 + CD4 + T cells, CD3 + CD8 + T cells, NK cells, B cells and CD4/CD8 ratio were analyzed. h4>Results: /h4>: After 6-week induction therapy, the percentage of CD3 + T cells, CD3 + CD4 + T cells and CD4/CD8 ratio were significantly increased, while CD3 + CD8 + T cells and B cells were decreased. CD3 + CD8 + T cells and B cells were closely related to BRAF V600E and MAP2K1 mutation. ∆CD3 + T cells, ∆CD3 + CD4 + T cells, ∆CD3 + CD8 + T cells, ∆NK cells and ∆B cells were related to treatment efficacy. As for organ involvements, ∆CD3 + T cells and ∆CD3 + CD8 + T cells were related to liver involvement, ∆CD4/CD8 ratio was related to CNS involvement ∆CD3 + T cells and ∆B cells were related to BRAF V600E mutation, while ∆CD3 + CD4 + T cells was related to MAP2K1 mutation. Furthermore, increased ∆CD3 + T cells, decreased ∆CD3 + CD4 + T cells, decreased ∆CD3 + CD8 + T cells, decreased ∆NK cells and increased ∆B cells were predictors for superior PFS, while increased ∆CD3 + T cells, decreased ∆CD3 + CD8 + T cells and decreased ∆NK cells were predictors for superior OS. In addition, multivariate Cox regression analysis showed that ∆CD3 + T cells and ∆CD3 + CD8 + T cells were independent prognostic factors for PFS. h4>Conclusions: /h4>: The peripheral lymphocyte subsets including CD3 + T cells, CD3 + CD4 + T cells, CD3 + CD8 + T cells, NK cells and B cells might be promising predictive indicators for LCH in children.