Publications by authors named "Udo S Gaipl"

Background: Low-grade endometrial stromal sarcoma (LG-ESS) is a rare uterine malignancy characterized by its complex tumor microenvironment (TME) and high recurrence rates, posing challenges to accurate prognosis and effective treatment. Identifying prognostic biomarkers is essential for improving patient stratification and guiding therapeutic strategies.

Methods: Using single-cell transcriptome analysis combined with H&E and multiplex immunofluorescence staining, we identified a subpopulation of tumor cells in LG-ESS and further validated the association of this subpopulation and its characteristic genes with LG-ESS prognosis by molecular characterization and bulk transcriptome data.

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Radiotherapy showed synergy with immunotherapy, yet the comparative effectiveness of combining immunotherapy (iRT) or chemotherapy (CRT) after platinum therapy failure in advanced non-small cell lung cancer (NSCLC) remains unexplored. We analyzed 163 patients (iRT:  = 120 vs. CRT:  = 43) eligible for combination radiotherapy.

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Background: Promptable foundation auto-segmentation models like Segment Anything (SA, Meta AI, New York, USA) represent a novel class of universal deep learning auto-segmentation models that could be employed for interactive tumor auto-contouring in RT treatment planning.

Methods: Segment Anything was evaluated in an interactive point-to-mask auto-segmentation task for glioma brain tumor auto-contouring in 16,744 transverse slices from 369 MRI datasets (BraTS 2020 dataset). Up to nine interactive point prompts were automatically placed per slice.

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Article Synopsis
  • The study explores the challenge of treating head and neck tumors due to their low radiosensitivity and investigates whether small molecule kinase inhibitors (smKIs) can enhance the effectiveness of radiotherapy by altering immune-related factors in tumor cells.
  • The researchers combined ATM and ATR inhibitors with a specific radiotherapy regimen and examined various effects, including tumor cell death, immune checkpoint marker expression, and cytokine release using cell lines with different HPV statuses.
  • Results showed that while the combination therapy effectively induced cell death, particularly with ATR inhibitors, it also altered the immune profile of surviving cancer cells, suggesting a complex interaction between treatment types and immune responses.
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The approval and effectiveness of immune checkpoint inhibitors in head-and-neck squamous cell carcinoma (HNSCC) highlights the role of the immune system in this tumor entity. HNSCCs not only interacts with the immune system in the tumor tissue, but also induce systemic effects that may be additionally influenced by further factors such as the microbiome. Nonetheless, reliable immunological biomarkers that predict treatment response and outcome in HNSCC patients are lacking.

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Background: This research aims to improve glioblastoma survival prediction by integrating MR images, clinical, and molecular-pathologic data in a transformer-based deep learning model, addressing data heterogeneity and performance generalizability.

Methods: We propose and evaluate a transformer-based nonlinear and nonproportional survival prediction model. The model employs self-supervised learning techniques to effectively encode the high-dimensional MRI input for integration with nonimaging data using cross-attention.

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Antitumor immune responses are predominantly mediated by CD8+ cytotoxic T cells (CTLs). But immune-modulatory factors in the tumor microenvironment determine the effectiveness of these responses. In this issue, Wei and colleagues report a new role for CTL-derived IL3 in stimulating basophilic granulocytes to produce IL4, which, in turn, activates, reprograms, and stabilizes CTLs.

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Article Synopsis
  • * This study primarily focuses on whether primary human macrophages from blood can uptake polystyrene micro- and nanobeads (MNBs) and how they respond to it, by visualizing these processes using advanced microscopy techniques.
  • * Findings revealed that the uptake of MNBs affects the metabolic activity of macrophages in a size- and concentration-dependent manner, increasing necrosis and reactive oxygen species (ROS) production, highlighting the need for further investigation into the effects of plastic pollution on human health.
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Unlabelled: In this randomized, placebo-controlled cross-over trial we aimed to investigate if radon spa therapy exerts more pain relief than exposure to warm water alone. In addition, immunological parameters were assessed in both treatment groups. In the RAD-ON02 trial, 116 patients suffering from musculoskeletal disorders (MSDs) received either serial radon spa or solely warm water baths.

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Musculoskeletal disorders (MSDs) are associated with pain and lead to reduced mobility and quality of life for patients. Radon therapy is used as alternative or complementary to pharmaceutical treatments. According to previous reports, radon spa leads to analgesic and anti-inflammatory effects, but the cellular and molecular mechanisms are widely unknown.

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Purpose: Individual prediction of treatment response is crucial for personalized treatment in multimodal approaches against head-and-neck squamous cell carcinoma (HNSCC). So far, no reliable predictive parameters for treatment schemes containing immunotherapy have been identified. This study aims to predict treatment response to induction chemo-immunotherapy based on the peripheral blood immune status in patients with locally advanced HNSCC.

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Cancer can affect all human organs and tissues and ranks as a prominent cause of death as well as an obstruction to increasing life expectancy. A notable breakthrough in oncology has been the inclusion of the immune system in fighting cancer, potentially prolonging life and providing long-term benefits. The concept of "immunotherapy" has been discussed from the 19th and early 20th centuries by Wilhelm Busch, William B.

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Purpose: Human papilloma virus (HPV) positive head and neck squamous cell carcinoma (HNSCC) tumors respond significantly better to anticancer treatments. It is assumed to be due to a better response to radiotherapy (RT), and presumably to an increased immunogenicity. However, little is known how the immune phenotype of HNSCC tumor cells is modulated by standard treatment, namely by radiochemotherapy (RCT).

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Purpose: Local tumor heating with microwave applicators has been used in multimodal breast cancer therapies. This hyperthermia allows to target small regions while marginally affecting healthy tissue. However, most preclinical examinations only use simplified heating methods.

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We introduce a deep-learning- and a registration-based method for automatically analyzing the spatial distribution of nodal metastases (LNs) in head and neck (H/N) cancer cohorts to inform radiotherapy (RT) target volume design. The two methods are evaluated in a cohort of 193 H/N patients/planning CTs with a total of 449 LNs. In the deep learning method, a previously developed nnU-Net 3D/2D ensemble model is used to autosegment 20 H/N levels, with each LN subsequently being algorithmically assigned to the closest-level autosegmentation.

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Background: Endogenous retrovirus (ERV) elements are genomic footprints of ancestral retroviral infections within the human genome. Previous studies have demonstrated that dysregulated ERV transcription level is associated with immune cell infiltration in cancers, but the association between ERV expression and programmed cell death protein 1 (PD-1) blockade response is currently unraveled for solid cancers, such as advanced clear cell renal cell carcinoma (ccRCC).

Methods: ERV mRNA profiles were obtained from three clinical trials of ccRCC where the patients were treated with anti-PD-1 (CM-009, CM-010, CM-025, and TCGA-KIRC data).

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Only a subset of patients with triple-negative breast cancer (TNBC) benefits from a combination of radio- (RT) and immunotherapy. Therefore, we aimed to examine the impact of radioresistance and brain metastasizing potential on the immunological phenotype of TNBC cells following hypofractionated RT by analyzing cell death, immune checkpoint molecule (ICM) expression and activation of human monocyte-derived dendritic cells (DCs). MDA-MB-231 triple-negative breast cancer tumor cells were used as model system.

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Macrophages are a vital part of the innate immune system that are involved in healthy biological processes but also in disease modulation and response to therapy. Ionizing radiation is commonly used in the treatment of cancer and, in a lower dose range, as additive therapy for inflammatory diseases. In general, lower doses of ionizing radiation are known to induce rather anti-inflammatory responses, while higher doses are utilized in cancer treatment where they result, next to tumor control, in rather inflammatory responses.

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Article Synopsis
  • The study explores the use of deep learning for autodelineation of head and neck lymph nodes to improve radiotherapy planning, highlighting the lack of existing public resources for this purpose.
  • A trained nnU-net model was evaluated using a cohort of CT images, with clinical experts comparing its segmentation against manually drawn contours.
  • Results showed no significant difference in quality ratings between deep learning and expert contours, but the inclusion of a CT slice plane adjustment improved the ratings for the deep learning segments.
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Article Synopsis
  • Radiotherapy for high-grade gliomas and brain metastases often leads to reactivation of cytomegalovirus (CMV), which can worsen neurological outcomes and prognosis, necessitating antiviral treatment.
  • This study explored the T cell distributions, specifically CD8+ T cells, in the blood of healthy individuals and glioma patients undergoing radiation therapy, aiming to identify a predictive marker for CMV reactivation.
  • Findings showed that patients with CMV reactivation had a higher percentage of CD8+ T cells, suggesting that measuring these cells could help predict CMV risk during brain RT, emphasizing the need to consider CMV status in T cell analyses.
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Melanoma is the most aggressive skin malignancy with high morbidity. Anti-programmed cell death protein 1 (PD-1) monotherapy has been applied in metastatic melanoma. However, still most of the patients do not respond to anti-PD-1 and the availability of the present approved biomarkers therefore is limited.

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