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...

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...

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...

ImportanceGenome-wide association studies have identified hundreds of common single nucleotide polymorphisms (SNPs) and small insertions/deletions (indels) associated with primary open-angle glaucoma (POAG) risk, though these variants have modest effect sizes and individually may have minor contributions to disease development. As whole-genome sequencing data is becoming more readily available, structural variants and other complex genomic features can be interrogated for contribution to disease...

Primary open-angle glaucoma (POAG) disproportionately affects individuals of African ancestry, yet rare coding variation in this population remains understudied. To address this gap, we performed a multi-cohort exome-wide meta-analysis across POAAGG, PMBB, All of Us, and UK Biobank, including 4,815 POAG cases and 22,922 controls of genetically inferred African ancestry. Although no gene reached exome-wide significance, we identified several suggestive gene-level associations driven by rare varia...

Immune effector cell-associated neurotoxicity syndrome (ICANS) is a common and life-threatening complication of chimeric antigen receptor (CAR) T-cell therapy, with early detection being critical for timely intervention and improved outcomes. Cytokines such as interleukin-6 (IL-6) are key mediators of the inflammatory cascade underlying ICANS pathogenesis, but prospective clinical evidence for their predictive value is limited. Here we quantify IL-6 levels in a prospective cohort of 40 CAR-T pat...

PurposeCirculating tumor DNA (ctDNA) analyses are informative as an early indicator of immunotherapy response in advanced non-small cell lung cancer (NSCLC); however, the clinical value of ctDNA molecular response requires further validation. Patients and MethodsAs part of a prospective clinical protocol (NCT05995821), we conducted targeted error-correction sequencing of ctDNA (n=328) and matched WBC DNA (n=109) from 109 patients with metastatic NSCLC who received anti-PD-(L)1 either as monothe...

Newly emerging influenza virus strains pose a constant threat as they encounter a population lacking neutralizing antibodies against the new strain. However, cross-reactive non-neutralizing antibodies (nnABs) may be present and assist in mitigating disease symptoms via various effector mechanisms, including antibody-dependent cellular cytotoxicity (ADCC). Although nnABs to influenza virus have received more attention lately, little information is available on their age-related prevalence, steady...

The phase 1b TICIMEL clinical trial evaluated the safety, tolerability, and anti-tumor activity of combining the immune checkpoint inhibitors (ICI), ipilimumab and nivolumab, with tumor necrosis factor (TNF) blockers, certolizumab or infliximab, to treat advanced melanoma patients. A higher proportion of responses was observed in patients receiving ICI and certolizumab, while patients treated with ICI and infliximab demonstrated superior tolerability. Moreover, CITE-Seq analyses of circulating C...

Allogeneic hematopoietic cell transplantation is the only curative option for many patients with acute myeloid leukemia (AML). In the current study, we designed and implemented a personalized assay, called v96, incorporating up to 96 mutations in 30 AML patients undergoing transplantation. The assay was performed on DNA derived in cells from the bone marrow as well as in cell-free plasma. All 30 (100%) of patients harbored molecular evidence of residual leukemia during remission that was detecta...

Immune imprinting, also known as immune history, is a core aspect of adaptive immunity that influences antibody responses to future antigen exposures. Nevertheless, the impact of sequential flavivirus vaccinations on epitope targeting and antibody activity in humans remains incompletely understood. This question is particularly important in regions where the inactivated Japanese encephalitis virus (JEV) vaccines and the live-attenuated dengue virus (DENV) vaccines are used, as both have been ass...

The gut microbiome composition varies across human populations, but its characteristics and determinants in a multi-ethnic setting remain incompletely understood. Singapore, a multicultural city-state, provides a context in which culturally diverse groups share a broadly similar built environment. Using the Health for Life in Singapore (HELIOS) cohort, we profiled the gut microbiome of ethnic Chinese, Indian, and Malay participants (n=861) who resided in the country. Despite substantial overlap ...

BackgroundTumor-associated macrophages (TAMs) display context-dependent functional polarization, but whether their prognostic impact is consistent across tumor types remains unclear. MethodsWe analyzed RNA-sequencing and clinical data from The Cancer Genome Atlas (TCGA) lung adenocarcinoma (LUAD; n=648), lung squamous carcinoma (LUSC; n=623), and melanoma (SKCM; n=466). Cox proportional hazards models adjusted for age and AJCC stage evaluated per-standard deviation (SD) expression of TAM marker...

Clinical interpretation of breast cancer sequencing is constrained not by a lack of data but by the absence of an organising framework that translates constellations of co-occurring mutations and copy-number alterations into tumour-level biology with prognostic and therapeutic meaning. This challenge is exemplified by PIK3CA, a clinically actionable alteration often treated as a single-label biomarker despite context-dependent associations with outcome. We analysed >5,000 breast tumours across m...

Clear cell renal cell carcinoma (ccRCC) is the leading cause of kidney cancer-related death, but how the tumor microenvironment shapes patient survival is not completely understood. Here, we describe the characterization of ccRCC tumor ecosystems from 498 patients using imaging mass cytometry with a focus on tumor, myeloid, and T cell landscapes. Data from more than 3 million single cells is analyzed using machine-learning to identify key ecosystem features that outperform basic clinical data fo...

Cancer heterogeneity is traditionally attributed to multiple parallel signaling pathways. This belief is challenged here by proposing the ER/PR axis as the dominant pathway underlying the full spectrum of breast cancer. Absolutely quantitated ER, PR, Her2 and Ki67 protein levels were accumulated over 8 years from 1652 specimens collected non-selectively and measured with Quantitative Dot Blot (QDB) method over time. Cox analysis showed ER and Ki67 as independent adverse prognostic factors while ...

This exploratory analysis of PAX LC, a Phase 2, 1:1 randomized, double-blind, superiority, placebo-controlled trial examined whether treatment with nirmatrelvir/ritonavir (NMV/r) versus placebo/ritonavir (PBO/r) in individuals with Long COVID could reveal immune features associated with symptom improvement. Eighty-two participants (n=45 PBO/r; n=37 NMV/r) provided blood samples at baseline (Day 0) and post-treatment (Day 28). Baseline demographic and immunological phenotypes were similar in the ...

T-cell lymphomas are often histologically indistinguishable from benign T-cell infiltrates. Clonality testing is frequently required for diagnosis. It lacks the spatial context and is slow and expensive, relying on complex, multiplexed PCR reactions, interpreted by experienced scientists or pathologists. We previously published details of a pair of highly specific monoclonal antibodies against the two alternatively used, but very similar, T-cell receptor {beta} constant regions, TCR{beta}1 and T...