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Systems-level immunomonitoring in children with solid tumors to enable precision medicine.

Cell

January 2025

Clinical Pediatrics Unit, Department of Women's and Children's Health, Karolinska Institutet, 17165 Stockholm, Sweden; Department of Immunology and Inflammation, Imperial College London, London W12 EH7, UK; Medical Research Council, Laboratory of Medical Sciences, Imperial College Hammersmith Campus, London, UK; Pediatric Rheumatology, Astrid Lindgren Children's Hospital, Karolinska University Hospital, 17176 Stockholm, Sweden. Electronic address:

Cancer is the leading cause of death from disease in children. Survival depends not only on surgery, cytostatic drugs, and radiation but also on systemic immune responses. Factors influencing these immune responses in children of different ages and tumor types are unknown.

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Dipeptidase 1 (DPEP1), initially identified as a renal membrane enzyme in mature human kidneys, plays a pivotal role in various cellular processes. It facilitates the exchange of materials and signal transduction across cell membranes, contributing significantly to dipeptide hydrolysis, glucose and lipid metabolism, immune inflammation, and ferroptosis, among other cellular functions. Extensive research has delineated the complex role of DPEP1 in oncogenesis and tumor progression, with its influence being context dependent.

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Background: Wilms tumor is one of the most common pediatric kidney cancers with poor prognosis. This study aims to explore the predictive values of lymph nodes (LNs), positive lymph node density (LND) and log odds of positive lymph nodes (LODDS) for the 5-year mortality of children with Wilms tumor.

Methods: The cohort study collected the data of 874 participants with Wilms tumor in the Surveillance, Epidemiology, and End Results (SEER) database.

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Background: In the fifth National Wilms Tumor Study, patients received vincristine and dactinomycin (VA) without radiation for stage I focal anaplastic Wilms tumor (FAWT) and VA plus doxorubicin (DD4A) and radiation for stage II-IV FAWT. Four-year event-free survival (EFS) and overall survival (OS) for stage I FAWT were 67.5% and 88.

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Background: Few studies have investigated associations between per- and polyfluoroalkyl substances (PFAS) and childhood cancers. Detectable levels of PFAS in California water districts were reported in the Third Unregulated Contaminant Monitoring Rule for 2013-2015.

Methods: Geocoded residences at birth were linked to corresponding water district boundaries for 10,220 California-born children (aged 0-15 years) diagnosed with cancers (2000-2015) and 29,974 healthy controls.

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