Longitudinal monitoring of Torque Teno virus DNAemia in kidney transplant recipients correlates with long-term complications of inadequate immunosuppression.

Optimization of individual immunosuppression, which reduces the risks of both graft loss and patients' death, is considered the best approach to improve long-term outcomes of renal transplantation. Torque Teno Virus (TTV) DNAemia has emerged as a potential biomarker reflecting the depth of therapeutic immunosuppression during the initial year post-transplantation. However, its efficacy in long-term monitoring remains uncertain. In a cohort study involving 34 stable kidney transplant recipients and 124 healthy volunteers, we established lower and upper TTV DNAemia thresholds (3.75-5.1 log10 cp/mL) correlating with T-cell activatability, antibody response against flu vaccine, and risk for subsequent serious infections or cancer over 50 months. Validation in an independent cohort of 92 recipients confirmed that maintaining TTV DNAemia within this range in >50% of follow-up time points was associated with reduced risks of complications due to inadequate immunosuppression, including de novo DSA, biopsy-proven antibody-mediated rejection, graft loss, infections, or cancer. Multivariate analysis highlighted "in-target" TTV DNAemia as the sole independent variable significantly linked to decreased risk for long-term complications due to inadequate immunosuppression (odds ratio [OR]: 0.27 [0.09-0.77]; p = 0.019). Our data suggest that the longitudinal monitoring of TTV DNAemia in kidney transplant recipients could help preventing the long-term complications due to inadequate immunosuppression.

Fusion-negative rhabdomyosarcoma 3D organoids to predict effective drug combinations: A proof-of-concept on cell death inducers.

Rhabdomyosarcoma (RMS) is the main form of pediatric soft-tissue sarcoma. Its cure rate has not notably improved in the last 20 years following relapse, and the lack of reliable preclinical models has hampered the design of new therapies. This is particularly true for highly heterogeneous fusion-negative RMS (FNRMS). Although methods have been proposed to establish FNRMS organoids, their efficiency remains limited to date, both in terms of derivation rate and ability to accurately mimic the original tumor. Here, we present the development of a next-generation 3D organoid model derived from relapsed adult and pediatric FNRMS. This model preserves the molecular features of the patients' tumors and is expandable for several months in 3D, reinforcing its interest to drug combination screening with longitudinal efficacy monitoring. As a proof-of-concept, we demonstrate its preclinical relevance by reevaluating the therapeutic opportunities of targeting apoptosis in FNRMS from a streamlined approach based on transcriptomic data exploitation.