Research articles

By integrating single-cell RNA and physically interacting cell sequencing analysis, here Cohen and colleagues report that neutrophils are enriched in physical crosstalk with breast tumor cells, promoting cancer aggressiveness.

Bilen et al. perform a phase 2 single-arm clinical trial of neoadjuvant cabozantinib in patients with locally advanced nonmetastatic clear cell renal cell carcinoma, assess efficacy and find antitumor CD8⁺ T cell response activation upon treatment.

Schrank et al. report the design and characterization of an antibody–toxin conjugate targeting CD47, promoting anti-tumor immunity in preclinical cancer models.

Marabelle et al. present updated data from the KEYNOTE-158 trial after ~4.5 years of follow-up, reporting an overall response rate of 34% and a median overall survival of 19.8 months in participants with MSI-H/MMR advanced noncolorectal solid tumors.

Bando et al. perform a phase II trial of atezolizumab monotherapy following platinum-based definitive chemoradiotherapy in patients with unresectable locally advanced esophageal squamous cell carcinoma and report a complete response rate of 42%.

Li et al. show through single-cell and functional data that tumor microenvironment remodeling promotes peritoneal metastasis of colorectal cancer through microbiome dysbiosis, neutrophil recruitment and mesenchymal transition of mesothelial cells.

Yang and colleagues present a small-molecule inhibitor for ADAR1 and show that its use is therapeutically beneficial in the context of prostate cancer.

Fan and colleagues show that FLASH radiation promotes proinflammatory polarization of tumor-associated macrophages, which in turn increases T cell influx in medulloblastoma and synergizes with CAR-T cell therapy.

Keyl et al. present an explainable artificial intelligence model-based real-world data analysis from over 15,000 patients across 38 cancer types, identified key prognostic marker interactions, and confirmed these in an external lung cancer cohort.

Ritter et al. present a spatial transcriptomics and deep learning-based approach named NePSTA (neuropathology spatial transcriptomic analysis) and leverage it to improve neuropathological diagnostics and enhance central nervous system tumor subtype classification.

Panzeri et al. use a Trim28^+/D9 mouse model with intrinsic developmental heterogeneity to show that ‘heavy’ and ‘light’ developmental morphs exhibit different timing, type and severity of cancer, linked to a relevant DNA hypomethylation signature.

Sanlorenzo et al. propose a strategy to boost immunotherapy by combining topically applied TLR7/8 agonists with systemic interferon-I, sensitizing dendritic cells to produce IL-12 for tumor clearance and an adaptive immune response at metastatic sites.

Whalen et al. report that increased DNA end resection in BRCA-deficient, PARP inhibitor-resistant cancers leads to increased sensitivity to DNA nicks, limiting tumor formation in mice, and propose the therapeutic exploration of nickases.

Puigserver and colleagues show that genetic targeting of specific mitochondrial respiratory complex I subunits in melanoma and breast cancer cells boosts tumor immune surveillance via upregulation of antigen-processing and presentation components.

Rudalska et al. describe a novel class of p38α inhibitors with increased target residence time. They explore the drugs’ specificity, pharmacokinetics and toxicity profile and show that they are efficacious in the context of colorectal cancer.

Rinnerthaler et al. perform a randomized phase 2 trial of neoadjuvant atezolizumab in combination with dual HER2 blockade plus epirubicin in patients with early HER2-positive breast cancer and report positively on efficacy and safety.

Ressler et al. perform a phase II clinical trial of neoadjuvant talimogene laherparepvec in cutaneous basal cell carcinoma and report on treatment safety, efficacy and on treatment-induced immune tumor microenvironment changes.

Jiang and colleagues identify ETV7 as a transcriptional node that skews CD8⁺ T cell transcriptional profiles toward exhaustion, consequently limiting antiviral and antitumor efficacy, and show that it can be targeted in CAR T cells to enhance efficacy.

Liang et al. study the impact of ERα antagonist/degraders against different Esr1 mutations in murine models and find that inhibition of mutant ERα induces lineage plasticity, which is also observed in Esr1-wild-type mice with long-term estrogen deprivation.

Shukla and colleagues study the genomic and transcriptomic data of exceptional responders to immunotherapy in renal cell carcinoma and find that such responses could be related to tertiary lymphoid structures, clonal neoantigen load and altered metabolism.