2 research outputs found
A parallelized cellular Potts model that enables simulations at tissue scale
The Cellular Potts Model (CPM) is a widely used simulation paradigm for
systems of interacting cells that has been used to study scenarios ranging from
plant development to morphogenesis, tumour growth and cell migration. Despite
their wide use, CPM simulations are considered too computationally intensive
for three-dimensional (3D) models at organ scale. CPMs have been difficult to
parallelise because of their inherently sequential update scheme. Here, we
present a Graphical Processing Unit (GPU)-based parallelisation scheme that
preserves local update statistics and is up to 3-4 orders of magnitude faster
than serial implementations. We show several examples where our scheme
preserves simulation behaviors that are drastically altered by existing
parallelisation methods. We use our framework to construct tissue-scale models
of liver and lymph node environments containing millions of cells that are
directly based on microscopy-imaged tissue structures. Thus, our GPU-based CPM
framework enables in silico studies of multicellular systems of unprecedented
scale.Comment: 29 pages, 11 figures, 3 table
Homologous recombination repair deficient prostate cancer represents an immunologically distinct subtype
Homologous recombination repair deficiency (HRD) is observed in 10% of patients with castrate-resistant prostate cancer (PCa). Preliminary data suggest that HRD-PCa might be more responsive to immune checkpoint inhibitors (ICIs). In this study, we compare the tumor immune landscape and peripheral T cell receptor (TCR) repertoire of patients with and without HRD-PCa to gain further insight into the immunogenicity of HRD-PCa. Immunohistochemistry was performed on tumor tissue of 81 patients, including 15 patients with HRD-PCa. Peripheral TCR sequencing was performed in a partially overlapping cohort of 48 patients, including 16 patients with HRD-PCa. HRD patients more frequently had intratumoral CD3+, CD3+CD8−FoxP3− or Foxp3+ TILs above median compared to patients without DNA damage repair alterations (DDRwt; CD3+ and Foxp3+: 77% vs 35%, p = .013; CD3+CD8−FoxP3−: 80% vs 44%, p = .031). No significant difference in CD8+ TILs or PD-L1 expression was observed. In peripheral blood, HRD patients displayed a more diverse TCR repertoire compared to DDRwt patients (p = .014). Additionally, HRD patients shared TCR clusters with low generation probability, suggesting patient-overlapping T cell responses. A pooled analysis of clinical data from 227 patients with molecularly characterized PCa suggested increased efficacy of ICIs in HRD-PCa. In conclusion, patients with HRD-PCa display increased TIL density and an altered peripheral TCR repertoire. Further research into the efficacy of ICIs and the presence of shared neoantigens in HRD-PCa is warranted