Biology subjects

Juul, R. I.

Publications and source records attributed to Juul, R. I..

3 recordsLinked to original sources

bioRxiv2026

Preoperative thymic output and T cell repertoire diversity are associated with recurrence after nephrectomy for localized renal cell carcinoma

Radiographic thymic health and peripheral T-cell repertoire features have been linked to outcomes in renal cell carcinoma (RCC), but their prognostic value after curative-intent surgery is unclear. We quantified preoperative blood signal-joint T-cell receptor excision circles (sjTRECs), a marker of thymic output, in 218 patients with localized RCC undergoing nephrectomy and characterized T-cell receptor {beta} (TCR{beta}) repertoires in 201 patients. We assessed overall survival (OS) and recurrence-free survival (RFS) using Kaplan-Meier and Cox models adjusted for age, sex, and Leibovich risk group. High sjTREC levels were associated with longer RFS after adjustment for age, sex, and Leibovich risk group (hazard ratio [HR] 0.50; 95% confidence interval [CI], 0.29-0.87; p=0.015), with a concordant OS estimate (HR 0.62; 95% CI, 0.38-1.02; p=0.058). sjTREC provided additional prognostic information beyond Leibovich risk stratification for recurrence overall and among intermediate/high-risk patients (likelihood-ratio test, p=0.024 and p=0.034, respectively). Higher TCR{beta} diversity was associated with longer RFS overall (HR 0.76; 95% CI, 0.60-0.96; p=0.024) and among intermediate/high-risk patients with longer RFS (HR 0.71; 95% CI, 0.55-0.92; p=0.009) and OS (HR 0.80; 95% CI, 0.65-0.98; p=0.031). Preoperative sjTREC provided prognostic information beyond clinicopathological risk, with higher TCR{beta} diversity associated with favorable outcomes.

cancer biology↗

bioRxiv2024

Comprehensive characterization of the T cell receptor repertoire in bladder cancer

T cells are one of the primary effector cells in the endogenous defense against cancer, yet the clinical impact of their quantity, diversity, and dynamics remains underexplored. Here we investigated the clinical relevance of the T cell receptor (TCR) repertoire in patients with bladder cancer. In advanced-stage bladder cancer, low pre-treatment peripheral TCR diversity was associated with worse overall survival (p=0.024), particularly when it coincided with a low fraction of circulating T cells (p=0.00049). The low-diversity TCR repertoires were dominated by expanded clones that persisted throughout treatment and disproportionately targeted latent viral infections. Longitudinal analysis revealed a reduction in TCR diversity after treatment indicating an adverse effect on the immune system. In early-stage bladder cancer, we showed that immunotherapy had a stimulatory effect on TCR diversity in patients with good outcomes. Single-cell sequencing identified most expanded clones as cytotoxic T cells, while non-expanded clones were predominantly naive T cells. Overall, our findings suggest that TCR diversity is a promising new biomarker that may offer new avenues for tailored oncological treatment to enhance clinical outcomes for bladder cancer patients.

cancer biology↗

bioRxiv2021

Sequence dependencies and mutation rates of localized mutational processes in cancer

BackgroundCancer mutations accumulate through replication errors and DNA damage coupled with incomplete repair. Individual mutational processes often show strong sequence and regional preferences. As a result, some sequence contexts mutate at much higher rates than others. Mutational hotspots, with recurrent mutations across cancer samples, represent genomic positions with elevated mutation rates, often caused by highly localized mutational processes. ResultsWe analyze the mutation rates of all 11-mer genomic sequence contexts using the PCAWG set of 2,583 pan-cancer whole genomes. We further associate individual mutations and contexts to mutational signatures and estimate their relative mutation rates. We show that hotspots generally identify highly mutable sequence contexts. Using these, we show that some mutational signatures are enriched in hotspot sequence contexts, corresponding to well-defined sequence preferences for the underlying localized mutational processes. This includes signature 17b (of unknown etiology) and signatures 62 (POLE), 7a (UV), and 72 (linked to lymphomas). In some cases, the mutation rate increases further when focusing on certain genomic regions, such as signature 62 in poised promoters, where the mutation is increased several thousand folds over the overall data set average. ConclusionWe summarize our findings in a catalog of localized mutational processes, their sequence preferences, and their estimated mutation rates.

cancer biology↗