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.

Aquaporins are a family of ubiquitously expressed transmembrane water channels implicated in a broad range of physiological functions. We have previously reported that aquaporin 4 (AQP4) is expressed on T cells and that treatment with a small molecule AQP4 inhibitor significantly delays T cell mediated heart allograft rejection. Using either genetic deletion or small molecule inhibitor, we show that AQP4 supports T cell receptor mediated activation of both mouse and human T cells. Intact AQP4 is required for optimal T cell receptor (TCR)-related signaling events, including nuclear translocation of transcription factors and phosphorylation of proximal TCR signaling molecules. AQP4 deficiency or inhibition impairs actin cytoskeleton rearrangements following TCR crosslinking, causing inferior TCR polarization and a loss of TCR signaling. Our findings reveal a novel function of AQP4 in T lymphocytes and identify AQP4 as a potential therapeutic target for preventing TCR-mediated T cell activation.
© The Author(s) 2023. Published by Oxford University Press on behalf of Society for Leukocyte Biology. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.