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Turajlic and colleagues assess longitudinal antibody and cellular immune responses against SARS-CoV-2 variants of concern in patients with cancer, following either recovery from SARS-CoV-2 infection or vaccination, in two back-to-back reports from the CAPTURE study.
Using in vivo models and human cancer datasets, Yang and colleagues identify a role for the epigenetic regulator Rnf2 in repressing the antitumor immune responses of natural killer and CD4+ T cells.
Straussman and colleagues undertake clonal analyses and show that drug tolerance to EGFR therapy in lung cancer cell populations is an inherited continuous trait that is determined by IRS1 phosphorylation.
Klemm et al. show that resistance to CSF1R inhibition in breast cancer brain metastasis is driven by compensatory activation of the CSF2Rb–STAT5 axis in macrophages, which can be alleviated by combined targeting of CSF1R and STAT5.
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.
Van Allen and colleagues develop a data-integration framework with an underlying knowledge base supporting clinical decision making and also serving as a hypothesis-generating platform, which the authors benchmark and validate across several retrospective cohorts and a prospective precision oncology trial.
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.
Italiano and colleagues demonstrate the utility of mature tertiary lymphoid structures to predict response to immunotherapy, with pathologic analysis in three independent patient cohorts spanning multiple tumor types.
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.
Wu and colleagues develop a barcoding tool, ClonMapper, which permits single-cell lineage tracing and clonal isolation and demonstrate its utility to study clonal dynamics in human CLL cells in the context of chemotherapy treatment and resistance.