Research articles

Han et al. show that SMARCA5 is required for the sustained expression of genes required for malignancy in pancreatic cells with mutant KRAS. Inhibiting SMARCA5 activity prevents malignant transformation while maintaining pancreatic regeneration.

Wang and colleagues report the clinical results and immunological correlates of a phase 2 clinical trial of cryoablation plus lenvatinib and sintilimab in persons with advanced or metastatic intrahepatic cholangiocarcinoma.

Tao et al. show that SCRN1 acts as a scaffold to facilitate GPX4 phosphorylation by STK38, thereby preventing chaperone-mediated autophagy of GPX4 and subsequent ferroptosis in patient-derived organoids and mouse models for hepatocellular carcinoma.

Majzner and colleagues show that engineering T cells with a membrane-tethered version of the signaling adaptor molecule SLP-76 alongside a chimeric antigen receptor (CAR) enhances CAR T cell activity against low-antigen-density tumors.

Qian and colleagues show that MEF2D⁺ cancer precursors reprogram liver-resident Kupffer cells to create a microenvironment supporting liver tumorigenesis.

Zhao et al. used single-cell and spatial multiomics data analysis of human and mouse lung adenocarcinoma tumors and cell lines to reveal TP53 mutation-associated changes in cancer cells and their microenvironment.

Sandén et al. report that the ligand signaling lymphocyte activation molecule family member 6 protects acute myeloid leukemia cancer cells from T cell-mediated killing, leading to immune escape, and show that this can be targeted by a blocking antibody.

Using mouse pancreatic cancer models, Tsanov et al. show that reactivation of SMAD4 at metastatic sites promotes tumor growth in the lung through RUNX1 but restrains metastatic growth through KLF4 in the liver, influenced by organ-specific epigenetic states.

Shao et al. developed an MRI–pathology-based foundation model to assess the pathology of prostate cancer for diagnosis and grading of tumors. The model is noninvasive and outperforms current pathological assessments.

Cangkrama et al. show that tumor cells from various cancer types use the mitochondrial trafficking protein MIRO2 and nanotubes to transfer mitochondria into surrounding fibroblasts, thereby inducing cancer-associated fibroblast differentiation and subsequent tumor growth.

Lu et al. characterize cis-regulatory element dynamics at different stages of colorectal cancer progression and identify a functional variant associated with increased colorectal cancer risk because of selective transcription factor binding.

Han et al. present TabulaTIME, a multicancer scRNA-seq resource, and report enrichment of extracellular matrix-related CTHRC1⁺ cancer-associated fibroblasts in proximity to SLPI⁺ macrophages, creating a profibrotic ecotype associated with tumor immunity.

Wang et al. designed sphingomyelin-derived vesicles that deliver paclitaxel to tumor site, improving its therapeutic efficacy and reducing associated toxicities, in mouse models of breast and pancreatic cancers.

Li and colleagues report that a septo-enteric polysynaptic circuit that is activated by chronic stress links the brain to the tumor microenvironment to promote colorectal cancer growth.

Vallentgoed et al. integrate clinical and multiomic data from persons with matched initial and recurrent IDH-mutant astrocytomas to identify progression-associated mechanisms and report a DNA methylation-based signature associated with survival.

Lightbody et al. present SWIFT-seq, a single-cell RNA sequencing approach to profile circulating tumor cells from patients with multiple myeloma and its precursor conditions and leverage it to derive clinical and biological insights into the disease.

Huang et al. analyzed serial samples from participants with metastatic non-small cell lung cancer treated with radiotherapy followed by immunotherapy and report improved clinical outcomes and enhanced antitumor responses in immunologically cold tumors.

Klebanoff and colleagues report that survival and persistence of CAR-T and CAR-NK cells are regulated by a FAS ligand–FAS autoregulatory circuit, showing that disabling FAS signaling enhances their antitumor efficacy in preclinical models.

Petroni et al. report that the infiltration of IL-17A-secreting γδ T cells in the tumor microenvironment coupled with the accumulation of immunosuppressive macrophages is associated with resistance to CDK4/CDK6 inhibition in HR⁺HER2⁻ breast cancer.

Cibula et al. present survival results of the SENTIX trial and demonstrate that SLN biopsy alone does not increase the risk of disease recurrence in patients with early-stage cervical cancer.