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Watson et al. demonstrate that astrocyte mitochondria can be horizontally transferred to glioblastoma cells in a GAP43-dependent manner, leading to changes in mitochondrial respiration and metabolism that promote proliferation and tumor growth.
Culbertson et al. profile antisense RNAs using a newly developed computational pipeline and identify NQO1-AS as contributor to breast cancer progression and lung metastasis through regulation of the redox enzyme NQO1.
Ruscetti and colleagues show that the pancreatic cancer tumor microenvironment suppresses immune surveillance following therapy-induced senescence via repression of inflammatory gene expression through EZH2.
Bassani-Sternberg and colleagues perform multiregion immunopeptidomics, genomics and spatial transcriptomics in patient lung cancer samples, demonstrating heterogeneity in the immunopeptidome associated with degrees of immune cell infiltration.
Akkari and colleagues find that CD103+ regulatory T cells are highly abundant in the glioblastoma environment after checkpoint blockade restraining therapy response, and show therapeutic benefit for combined Treg targeting with radio-immunotherapy.
Getz and colleagues demonstrate a computational approach to estimate the timing of genomic drivers in early tumor progression from cancer types that do not have premalignant disease, using HPV-negative and HPV-positive head and neck squamous cell carcinoma as examples.
Voorwerk et al. report the clinical and translational results from a phase II trial evaluating the combination of carboplatin with anti-PD-L1 in patients with invasive lobular breast cancer, who have been underrepresented in clinical trials so far.
Nabbi et. al. analyze immunohistochemistry, comprehensive genomic profiling, RNA-sequencing, and TCR-sequencing data from 66 pediatric patients with cancer from a phase 1–2 clinical trial (iMATRIX-atezo) to nominate biomarkers associated with response to immunotherapy in pediatric cancer.
Beltran and colleagues examine the underlying mechanisms behind the observed heterogeneous expression of the prostate cancer drug target and biomarker, PSMA, in castration-resistant prostate cancer, involving regulatory roles of both HOXB13 and AR.
Sun et al. identify the deubiquitinase USP15 as a regulator of PARP1 stability in triple-negative breast cancer and show that the hormone receptors ER, PR and HER2 inhibit USP15-mediated PARP1 stabilization, modulating base excision repair.
Schellenberger and colleagues engineer masked, conditionally active T-cell engagers targeting tumor antigens and CD3 and show potent, protease-dependent antitumor activity in mouse models, as well as safety in non-human primates.
Su et al. find that BACH1 specifically interacts with the p53 (R175H) hotspot mutant. This has double oncogenic effects, leading to increased expression of the pro-metastatic targets of BACH1 as well as blockage of its capacity to activate ferroptosis.
Park et al. show that in the process of metastasis, dying tumor cells enhance the outgrowth of their surviving counterparts via nuclear expulsion, resulting in an extracellular DNA–protein complex that activates RAGE receptors on tumor cells.
Using single-cell and high-dimensional profiling of the immune microenvironment, Vignali and colleagues uncover distinct cell subsets and interactions in human invasive ductal and lobular breast carcinoma, with potential prognostic and therapeutic relevance.
Shi et al. report a sulfonation-dependent vulnerability of liver tumors expressing the sulfotransferase SULT1A1 by showing their sensitivity to the small molecule YC-1 and identifying structurally related compounds that can be modified by SULT1A1.
Turrell et al. show that, in young mice, low-level PDGF-C expression maintains dormancy of disseminated tumor cells, but, in aged or fibrotic lungs, the PDGF-C-high environment promotes proliferation, which can be counteracted with inhibition of PDGFRα or PDGF-C blockade.
Wu et al. report that IFNγ induces the phase separation of KAT8 and IRF1 into condensates that promote PD-L1 upregulation. They further identify a peptide that blocks KAT8–IRF1 condensates, reducing PD-L1 levels and increasing antitumor immunity.
Adler et al. identify granulocyte-derived lipocalin-2 as a mediator of inflammatory astrocyte activation, which in turn facilitates brain metastasis in breast cancer and melanoma.
Coppé and colleagues define a resistance mechanism to combination BRAF- and EGFR-targeted therapy in BRAFV600E colorectal cancers that could be overcome in vitro and in vivo by repurposing COX2 inhibitors.
Fendt and colleagues find that pre-metastatic niche formation and a high-fat diet increase palmitate availability in future organs of metastases and show that breast cancer cells use palmitate to generate acetyl-CoA, acetylate the NF-κB subunit p65 and induce pro-metastatic signaling.