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Jacks and colleagues demonstrate the effects of neoantigen expression level on T-cell priming and immune surveillance during tumor development and progression and explore implications for immunotherapies, using in vivo models of colorectal cancer.
Pappalardi and colleagues identify a potent noncovalent DNMT1-selective inhibitor with improved tolerability and efficacy in preclinical AML models compared with clinically validated covalent pan-DNMT inhibitors.
Mizukoshi and colleagues use patient samples and xenotransplants to show that the microbiota associated with chronic liver disease promote liver carcinogenesis through gelE-positive Enterococcus faecalis via induction of TLR4–Myd88 signaling.
Dotti and colleagues present a CAR design featuring trans-acting CD28 and 4-1BB co-stimulation and shared CD3ζ-chain, which improved CAR-T cell metabolic and antitumor functions and avoided tumor escape through simultaneous targeting of two antigens.
Mittal and colleagues investigate the mechanisms underlying the therapeutic effects of radiation therapy in combination with checkpoint blockade, finding a role for activated lung-resident secretory club cells in modulating antitumor immune responses.
Shi and colleagues show that PUS7 controls tRNA pseudouridylation and codon-specific translation to fuel glioblastoma tumorigenesis, and discover a PUS7 inhibitor that delays tumor growth in glioblastoma models.
Tanaka and colleagues perform a comprehensive multi-omic characterization of peritoneal metastasis of gastric cancer to define molecular subtypes and actionable therapeutic targets.
Chinnaiyan and colleagues perform a high-throughput compound screen and identify PIKfyve inhibition as a therapeutic strategy to enhance immune checkpoint blockade responses in advanced prostate cancer.
Yarchoan and colleagues present a single-arm phase 1 clinical trial of cabozantinib with immune checkpoint inhibition for patients with hepatocellular carcinoma. Using high-dimensional spatial analysis, they identify immune features enriched in responders.
Zhou and colleagues demonstrate that thiopurine chemotherapy in mismatch repair-deficient ALL cells leads to R248Q TP53 mutations and clonal selection that favors on-treatment ALL relapse and chemoresistance.
Morin and colleagues develop a data-integration framework capable of performing continuous learning from electronic health records on clinical, social and demographic data collected over a decade to estimate pan-cancer survival prognosis.
Drake and colleagues demonstrate that castration in prostate cancer models promotes IL-8 secretion and immunosuppressive myeloid-derived suppressor cell migration, and that inhibiting this axis in combination with checkpoint blockade can mitigate tumor progression.
Obenauf and colleagues report that acquired resistance to BRAF and MEK inhibitors in melanoma confers cross-resistance to immune checkpoint blockade by fostering a cancer cell–instructed, immune-evasive tumor microenvironment.
Manczinger and colleagues define ‘promiscuity’ as a feature of HLA-I alleles representing peptide repertoire breadth; promiscuous alleles may promote a more tolerant tumor microenvironment and negatively impact tumor immune surveillance.
Kharas and colleagues identify the RNA-binding proteins RBMX and RBMXL1 as AML tumor promoters that alter chromatin compaction and hence cell survival via transcriptional regulation of the heterochromatin protein encoded by CBX5.
Enver and colleagues report that epigenetic cell state, rather than genetic diversity, drives bottleneck selection of subclonal genotypes during induction chemotherapy in childhood B-cell precursor acute lymphoblastic leukemia.
Huber and colleagues utilize a multi-omic analytical pipeline to define an axis of proliferative drive involving mTOR, MYC and OXPHOS metabolic activity that is associated with disease heterogeneity and outcome in clinical cohorts of CLL.
Fuks and colleagues report that downregulation of the FTO m6A RNA demethylase activates the Wnt pathway, promoting EMT-mediated progression of epithelial tumors and conferring sensitivity to Wnt inhibitors.
D’Andrea and colleagues identify the antibiotic novobiocin as a specific POLQ inhibitor with preclinical activity in homologous-recombination-deficient breast and ovarian tumors in vivo, including these with acquired PARP inhibitor resistance.
Bild and colleagues identify convergent clonal evolution mechanisms through single-cell genomic analyses, explaining therapy resistance in patients with early-stage breast cancer treated with endocrine and CDK4/6 therapy in the FELINE trial.