Cell Reports

BackgroundPATZ1 fusion-positive central nervous system (CNS) tumors frequently harbor MN1::PATZ1 fusions as driver mutations, provisionally classified as a rare DNA methylation class of low-grade neuroepithelial tumors. Radiographically, they resemble pilocytic astrocytomas with tumor and cystic components, but their supratentorial cortex location and higher recurrence rates are distinguishing features. An intermediate clinical course, despite focal high-grade histopathology, underscores the nee...

Reliable non-invasive biomarkers for tumor grading and disease monitoring in pediatric brain tumors are an unmet clinical need. Circulating extracellular vesicles (EVs) carrying molecular cargo reflective of tumor biology, offer promise as liquid biopsy tools. We have previously discovered EV-associated Syndecan-1 (SDC1) to be overexpressed in malignant brain tumors, but its value as a biomarker in pediatric disease remains unclear. In this study, plasma EVs were isolated from pediatric brain tu...

Examining LncRNA-driven cancer biology, our study represents the first comprehensive investigation of the LncRNA CDKN2B-AS1 across multiple cancer types, revealing its genetic basis for cancer susceptibility, and associations with thromboembolic risks and immunological dynamics. Stratification across hematological and non-hematological cancers revealed predominant prevalence rates of the CDKN2B-AS1 C-allele, notably higher in solid tumor malignancies, peaking at 86.8% in colorectal carcinoma (CR...

BackgroundMalignant pediatric brain tumors remain the leading cause of cancer-related mortality in children. Current diagnostics rely on imaging and invasive biopsy, which may not capture tumor heterogeneity. Liquid biopsy-based biomarkers such as tumor-educated platelets have shown diagnostic value in adult cancers, but their utility in pediatric brain tumors has not been investigated. MethodsWe analyzed platelet transcriptomes of 73 blood samples from 23 pediatric brain tumor patients, classi...

In approximately one third of patients, resected head and neck squamous cell carcinoma will recur. We postulated that the induction of tumor neoantigen-specific T cell responses could prevent relapse. To this end, we developed TG4050, an individualized neoantigen therapeutic vaccine encoding up to 30 patient-specific predicted tumor neoantigens delivered by a Modified Vaccinia Ankara virus viral vector. We tested TG4050 as single agent in a randomized phase I trial. We found that of 16 evaluable...

Regional lymph nodes (LNs) in the thoracic cavity serve as essential immunological hubs that coordinate humoral and cell-mediated responses against the development and progression of non-small cell lung cancer (NSCLC). To investigate immune dysregulation in the non-metastatic regional LNs of patients with aggressive NSCLC, we performed multimodal profiling on 36 LNs from 11 patients undergoing curative-intent resection including CITE-seq, scRNA-seq, and Imaging Mass Cytometry (IMC). Regional N1 ...

BackgroundLong-term fasting is a promising strategy for improving human health and reducing cardiometabolic risk. Emerging evidence suggests that the gut microbiome may mediate many of these benefits, but the role of its viral component, dominated by bacteriophages, remains poorly understood. MethodsUsing shotgun metagenomic data from a single-arm, monocentric fasting intervention, this study profiled the gut virome (n=89 individuals, n=241 samples) before and after 9.8 days of fasting ([~]250 ...

DNA repair capacity (DRC), particularly at the pathway level, varies among individuals. While previous studies explored DRC in relation to environmental exposures and cancer risk, few measured DRC in patient-focused cohorts and were focused on one or two repair pathways only. We comprehensively profiled DRC for all the major repair pathways and DNA lesions in 100 lung cancer patients undergoing radiotherapy (RT) using advanced Fluorescence Multiplex based Host Cell Reactivation assays in blood c...

Gastrointestinal (GI) polyposis is a major risk factor for colorectal cancer (CRC) and a defining feature of hereditary polyposis syndromes such as familial adenomatous polyposis (FAP). Therapy-associated polyposis (TAP), however, is a rare and incompletely characterized condition that develops decades after treatment for childhood or young adult cancers (CYAC), most often following abdominopelvic radiation or exposure to alkylating agents. As long-term CYAC survival improves, the burden of late...

BackgroundImmune checkpoint inhibition has transformed cancer therapy; however, many patients fail to respond to single-agent blockade, and combination strategies are often limited by toxicity. Central nervous system tumors exploit multiple immunosuppressive pathways, including the CD200 and PD-1/PD-L1 axis to evade anti-tumor immunity and support tumor aggressiveness. MethodsWe investigated ARL200, a peptide ligand targeting the CD200 activation receptor (CD200AR) using in vitro immune assays,...

An H3N2 variant, named subclade K, continues to circulate widely during the 2025-2026 influenza season. This virus possesses a hemagglutinin (HA) protein that has eleven substitutions relative to the HA of the Northern Hemisphere 2025-2026 H3N2 vaccine strain. Many of these substitutions are in epitopes in well-characterized HA antigenic sites. Despite this, interim vaccine effectiveness studies indicate that the 2025-2026 influenza vaccine provides moderate protection against H3N2 subclade K in...

Immune checkpoint inhibitors (ICIs) have transformed cancer treatment but commonly cause immune-related adverse events (irAEs), whether administered as monotherapy or in combination with other oncological agents. We present the first reported case of ICI-induced granulomatous sialadenitis in a male patient in his mid-fifties with BRAF-V600E-mutated papillary thyroid carcinoma who received sequential treatment with BRAF/MEK inhibitors followed by pembrolizumab. The patient experienced acute-onset...

TRAF1 is a pro-survival signaling adaptor that contributes to NF-{kappa}B activation downstream of a subset of TNFR superfamily members. TRAF1 is overexpressed in many cancers of mature B cells, including chronic lymphocytic leukemia (CLL). Previous studies have established that TRAF1 S146 is a target of phosphorylation by the kinase PKN1 and that PKN1 is required to prevent cellular inhibitor of apoptosis protein (cIAP)-dependent degradation of TRAF1 in the CD40 signaling complex. The kinase in...

Lung cancer remains the leading cause of cancer-related deaths worldwide, with tumor recurrence a major contributor to its high mortality. The genetic and molecular mechanisms of recurrence remain poorly understood. Using whole-exome sequencing of 155 primary non-small cell lung cancers, we studied the mutational landscape and driver alterations associated with recurrence. Primary tumors that developed recurrence had higher mutational burden, including hypermutated tumors explained by mutations ...

Pediatric solid high-risk malignancies mostly lack established molecular biomarkers for early detection, minimal residual disease assessment, or treatment monitoring. Challenges include small patient numbers, limited sample volumes, low tumor mutational burden, and few recurrent alterations. Within the prospective multicenter pediatric precision oncology program INFORM, we collected liquid biopsies from 130 pediatric patients and optimized cfDNA isolation and analysis. Whole-genome, whole-exome,...

Multiple myeloma (MM) evolves from monoclonal gammopathy of undetermined significance (MGUS) and smoldering MM (SMM) with annual progression rates of 1% and 10%, respectively. Current risk models dont fully capture the underlying dynamic molecular processes. We hypothesized that urinary peptides reflect disease-specific microenvironmental alterations in plasma cell dyscrasias. To test this hypothesis, capillary electrophoresis-mass spectrometry CE-MS was applied to profile the urinary peptidome ...

In this report, experiments were performed to assess how Arylsulfatase B (ARSB; N-acetylgalactosamine-4-sulfatase) treatment might interact with Pembrolizumab and improve therapeutic responses in melanoma. ARSB acts to remove 4-sulfate groups from chondroitin 4-sulfate (C4S; chondroitin sulfate A; CSA). ARSB is required for the degradation of C4S, identified as an oncofetal, tumor-agnostic antigen. Previous reports showed that in syngeneic B16F10 mouse melanomas, ARSB inhibited progression of su...

Post-treatment measurable residual disease (MRD) in acute myeloid leukemia (AML) patients is associated with adverse clinical outcomes. Validated molecular methods for AML MRD are preferable to flow cytometry assays but are not available for all patients. The limit of detection (LOD) of next-generation sequencing (NGS) assays for single nucleotide variants is restricted by technical error rates. Structural alterations are common genetic features of AML, but MRD approaches for detecting this clas...

A new H3N2 variant (named subclade K) possesses several key hemagglutinin substitutions and is circulating widely during the 2025-2026 influenza season. In this report, we completed experiments to determine if the 2025-2026 seasonal influenza vaccine elicits antibodies in humans that recognize this variant. We find that H3N2 subclade K viruses are antigenically advanced; however, the 2025-2026 seasonal influenza vaccine elicited antibodies in many individuals that efficiently recognized these vi...

ObjectiveTumor transformation is accompanied by widespread methylation changes, in the form of cytosine modifications, in transposable elements (TEs). The purpose of this study was to investigate whether changes in methylation and hydroxymethylation in the form of 5mC and 5hmC within transposable elements in circulating cell-free DNA (cfDNA) can serve as predictive markers of ovarian malignancy. MethodsHealthy women as well as women undergoing surgery for various benign, borderline, or malignan...