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The mechanism of macrophage cytotoxicity against cancer cells requires further illustration. By employing CRISPR screening in CAR-macrophage and cancer cell co-culture system, the authors identify depletion of ATG9A on cancer cells sensitizes them to macrophage-mediated killing, which can be synergic with CSF1R inhibition in cancer treatment.

Modifying the polyethylene glycol lipid ratio and phospholipids in the lipid nanoparticle component of nucleoside-modified mRNA–lipid nanoparticle vaccines is shown to have an impact on the elicited cellular and humoral immune responses.

As presented at the 2025 AACR Annual Meeting, in an ongoing first-in-human phase 1 trial of a next-generation KRAS-G12C inhibitor in patients with solid tumors, encouraging safety and response results were observed, including in patients with non-small-cell lung cancer.

The ratio between the levels of two synaptic proteins in cerebrospinal fluid predicts future cognitive resilience versus decline among presymptomatic individuals and individuals with early Alzheimer’s disease harboring amyloid and tau pathology.

A comparison of compatibilities in protospacer adjacent motifs and of on-target and off-target activities of Streptococcus pyogenes Cas9 variants at endogenous sites in human cells enables the editing of new genomic sites associated with genetic diseases.

JAK inhibitors display very good clinical responses in patients with myeloproliferative neoplasms, irrespective of JAK2 mutational status. Here, the authors discover that JAK inhibitors exert their anti-tumorigenic effects by targeting the bone marrow stroma and non-malignant hematopoietic cells instead of the oncogenic signaling in myeloproliferative neoplasms.

Exome sequencing of 851 trios from more than 2,500 individuals finds 187 genes with de novo mutations that contribute to meningomyelocele (spina bifida) and highlights critical pathways required for neural tube closure.

The role of bile acid receptor TGR5 in feeding regulation remains elusive. Here, authors show that physiological and pharmacological activation of TGR5 in the nucleus of the solitary tract lowers feeding and enhances leptin signaling in rats.

Jamaican fruit bats support disseminated infection of Ebola but not Marburg virus. The differences in infection dynamics are partially attributable to Marburg’s less efficient entry and impaired antagonism of type I interferon signaling.

Diffuse large B-cell lymphoma (DLBCL) is a heterogeneous disease group with CAR T cells offering therapeutic success in otherwise hard-to-treat cases. Here, authors study the in vivo expansion and persistence of CAR T cells in the peripheral blood of successfully treated DLBCL patients, demonstrating that two different CD8+ precursor phenotypes in the initial cell product give rise to two independent waves of clonally expanded CAR T cells with distinct phenotypes in peripheral blood.

A publicly accessible tool—the TIMES score—for predicting the risk of recurrence of hepatocellular carcinoma is revealed, providing mechanistic insights into the prognostic patterns for hepatocellular carcinoma.

Single-cell RNAseq can struggle to capture cellular heterogeneity due to the relatively low expression of biologically meaningful transcripts. Here the authors present an approach called scCLEAN, which uses CRISPR/Cas9 to target and remove certain ubiquitous transcripts, thereby enhancing the detection of low-abundance transcripts.

Reverse electron transport is the mechanism behind excess mitochondrial reactive oxygen species in the livers of obese mice, which has implications for developing therapeutics for fatty liver disease in humans.

Gene regulation in engineered microbial populations is often tuned at individual cell levels. Now, a population-wide amplification system has been devised that expands the dynamic range of plasmid transfer and gene regulation in bacteria.

Cancer incidence is rare in long-lived bats. Here the authors find that although bat fibroblasts express telomerase and require only two oncogenic hits for malignant transformation, bats may rely on elevated p53 signaling and enhanced immunosurveillance to prevent cancer.

PAM sequences without G bases can be edited with SpCas9 variants that were continuously evolved in the laboratory.

MicroRNAs regulate brain development and aging. Here, authors show that a spatio-temporal atlas of 15 mouse brain regions reveals sex- and region-specific microRNA patterns, including age-related microglial miR-155-5p increase targeting mTOR.

Loss-of-function variants in thyroid hormone transporter MCT8 cause a neurodevelopmental and metabolic disorder. Here the authors identify genotype-phenotype relationships, advance insights in MCT8 (dys)function and create a pathogenicity-severity variant classifier.

Genetic control of mosquito vector populations is a key tool for reducing malaria infections. Here, the authors develop a self-limiting strategy where CRISPR-Cas9 is inherited exclusively on the Y chromosome and drives an autosomal mutation resulting in dominant sterility in female offspring.

Chou et al. generate transdifferentiated human neurons from fibroblasts from young or aged individuals and patients with Alzheimer’s disease. Studies of endolysosomes and proteostasis suggest a role for lysosomal quality control in Alzheimer’s disease pathology.

A microglial state, featuring lipid droplets and secretion of neurotoxic factors, is shown to be most prominent in people with Alzheimer’s disease who have the APOE4 genotype.

While transition metal complexes bearing terminal oxido ligands are common, those of group 11 elements have yet to be experimentally observed. Here, Riedel and colleagues synthesise molecular oxygen fluorides of copper, silver and gold, and show that the oxo ligands possess radical character.

Puissant and colleagues identify a myeloid-restricted PIK3CG/p110γ–PIK3R5/p101 axis as a therapeutic vulnerability in acute myeloid leukemia and develop a proteolysis-targeting chimera to potently degrade PIK3CG and suppress AML progression.

Efficient production of MSC secretome for therapeutic applications remains a challenging task. Here, the authors present an approach whereby an acoustofluidic mechanobiological environment can form reproducible 3D MSC aggregates, allowing for secretome production with high efficiency.

Circulating cell-free DNA (cfDNA) assays for monitoring individuals with cancer typically use tumor-specific mutations that may not be detected in many patients. Here, the authors develop a tumor-independent and mutation-independent approach (DELFI-TF) to estimate tumor burden in cfDNA for treatment response monitoring and clinical outcome prediction.

Follicle stimulating hormone (FSH) has been shown to Alzheimer’s disease like pathology in rodent models. Here the authors show using cellular and animal models that ApoE4 and FSH collectively act to trigger AD-like pathogenesis, by activating C/EBPβ/δ-secretase signalling.

Here, Kessler et al use single-cell RNA sequencing of the intestine and mesentery from H18N11 influenza-infected bats to show that viral infection is predominant in leukocytes and causes activation of immune cells and antiviral gene signatures.

Blood vessel development depends upon endothelial cell migration and adhesion, which are regulated by Rho-GTPases. Here the authors identify Rho-GTPase guanine nucleotide exchange factors that specifically control lateral filopodial contacts and are required for lumen formation during angiogenesis.

The desmoplastic stroma constitutes part of the microenvironment in pancreatic ductal adenocarcinoma. Here the authors show that Class I HDACs regulate the pro-desmoplastic and pro-tumorigenic transcriptional programs to support stromal activation and tumour progression.

The cytokine IL-6 controls the survival, proliferation and effector functions of lymphocytes. Jones and colleagues show that activation of CD4⁺ T cells leads to suppression of STAT1 activation by tyrosine phosphatases and changes the effector characteristics of memory CD4⁺ T cells in response to IL-6.

Directed evolution creates new compact Cas9 variants that target most single pyrimidine nucleotide PAMs.

The integrated stress response (ISR) allows cells to restore cellular homeostasis upon a wide range of stress stimuli. Here, the authors show that PIM2 inhibition activates the ISR and promotes NOXA expression, in turn making tumour cells vulnerable to MCL1 inhibition.

TMEPro profiles the glycosylated secreted and plasma membrane proteome of 100 human pancreatic tissue samples, defines cell type origins and identifies potential paracrine cross-talk mediated through tyrosine phosphorylation.

Getting synthetic biology circuit-based sensors into field applications is still a challenge. Here the authors combine a circuit sensor with a glucose meter for small analyte and nucleic acid detection.

Here, the authors demonstrate that inhibition of PTP1B and PTPN2 in tumor cells and T-cells with a small molecule inhibitor represses the growth of immunogenic and cold tumors, and enhances response to anti-PD-1 immunotherapy without promoting immune-related toxicities.

Leukemic stem cells (LSCs) drive chemoresistance and relapse in acute myeloid leukemia. Here, the authors show that the splicing factor RBM17 supports LSCs through avoiding nonsense-mediated decay of pro-leukaemic factors such as the translation initiation factor EIF4A2.

Homing-based gene drives show promise for malaria control through reducing or modifying mosquito populations, but understanding gene drive mechanisms is vital for policy. Here, authors show minimal carryover of extra sequences with gene drives, and potential for mixed methods of gene drive inheritance.

In a large-scale, international, multicenter, phase 1/1b trial, treatment of patients with advanced solid tumors with the B7H3-targeting antibody–drug conjugate YL201 was safe and showed preliminary clinical efficacy.