Major Finding: A phase 1b trial demonstrated the safety of cretostimogene grenadenorepvec plus nivolumab in muscle-invasive bladder cancer (MIBC).Concept: Boosting immune checkpoint inhibition with on...

Major Finding: Lipids derived from ascites are taken up by NK cells and drive NK cell dysfunction in ovarian cancer. Concept: Polar lipids such as phosphatidylcholine disrupt NK plasma membrane order ...

Major Finding: ASXL1 regulates T-cell terminal differentiation and exhaustion during chronic antigen exposure.Concept: Disruption of ASXL1 alters histone ubiquitination to promote a stem-like effector...

Major Finding: HIV Nef expression reduces allorecognition and apoptotic cell death of CAR T cells.Concept: Controlled Nef expression reduces HLA-I levels and protects CAR T cells from CD8+ T cell– and...

Main Finding: HER2+ breast tumors and high-risk ER+ breast tumors share genomic features that reflect similar mechanisms of tumor evolution.Concept: The genomic architecture of breast cancer is constr...

Major Finding: PCSK9 regulates cholesterol uptake and controls the trajectory of metastasis to secondary organs in pancreatic ductal adenocarcinoma (PDAC). Concept: Cholesterol uptake supports mTORC1-...

Major Finding: Serotonin transporter depletes intratumoral serotonin which dampens CD8+ T-cell antitumor immunity.Concept: Serotonin transporter inhibition with SSRIs drives T-cell antitumor immunity ...

Main Finding: High-grade osteosarcomas frequently exhibit a loss–translocation–amplification (LTA) pattern of chromothripsis that inactivates TP53 and amplifies oncogenes.Concept: Ongoing chromothrips...

Major Finding: Digoxin treatment reduces circulating tumor cell cluster size in patients with metastatic breast cancer.Concept: Genes involved in cell–cell adhesion and cell cycle pathways are suppres...

Main Finding: A phase I clinical trial demonstrates the safety of GD2-targeted CAR T-cell therapy in H3K27M+ diffuse midline glioma.Concept: H3K27M+ diffuse midline gliomas express high levels of GD2,...

Major Finding: The liver X receptor (LXR) pathway drives intestinal regeneration and limits tumorigenesis.Concept: Transcriptomic and pharmacologic studies define a CYP27A1–LXR–TLS signaling axis in i...

Major Finding: APOBEC3-associated mutagenesis and ecDNA formation coordinately drive urothelial cancer evolution.Concept: ecDNA events enable adaptive resistance to chemotherapy.Impact: This study del...

Major Finding: RAF-independent MEK activation promotes histiocytic neoplasms that are sensitive to ERK inhibition.Concept: MEK1E102_I103del drives myelomonocytic expansion, hepatosplenomegaly, and an ...

Major Finding: An analysis of immune responses in children with cancer reveals the effects of age and tumor type. Concept: Pediatric tumors have varied mutational burden which correlates with immune c...

Major Finding: Cancer cells transfer mitophagy-resistant mitochondria to tumor-infiltrating lymphocytes (TIL) that impair antitumor activity. Concept: Deubiquitinase USP30 protects cancer cell-derived...

Major Finding: Molecular residual disease (MRD) preceded death or clinical recurrence in the ADAURA trial by nearly 5 months. Concept: Longitudinal MRD monitoring may stratify risk for patients with E...

Main Findings: Visugromab, a GDF-15 blocking antibody, is tolerable and elicits clinical responses in combination with nivolumab.Concept: GDF-15 may represent a mechanism of anti-PD-1 resistance that ...

Main Findings: Complete blood count indices are patient-specific and stable over decades in healthy adults.Concept: These hematologic setpoints are deep physiological phenotypes associated with variat...

Major Finding: Vaccinations against SARS-CoV-2 correspond with enhanced immunotherapy response in preclinical models and patients.Concept: mRNA vaccines increase Type I interferon signaling, T-cell priming and checkpoint blockade response.Impact: mRNA vaccines against non-tumor antigens could be used to sensitize immunologically cold tumors. Read the full article here