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In a systematic review and meta-analysis of nonrelapse mortality (NRM) following CAR T cell treatment in 7,604 patients with lymphoma and myeloma, almost half of cases were atrributable to infections and NRM estimates varied across both tumor types and CAR T cell products

Sodium glucose transporters are critical for maintaining glucose homeostasis. Here, authors provide a detailed framework for how SGLTs utilize cellular membrane potentials to stabilize their substrate accepting conformation leading to accelerated transport.

In an interim analysis of an ongoing phase 1 trial of CAR T cells targeting EGFR and IL13Ra2 in patients with multifocal, recurrent glioblastoma, intrathecal delivery is feasible and well tolerated, with some reductions seen in tumor size.

Testicular germ cell tumors are highly heritable, and the authors present the largest genome association study, identifying 22 novel loci, which account for a third of those identified to date. Implicated pathways include male germ cell development and differentiation, and chromosomal segregation.

Eosinophilic esophagitis (EoE) is characterized by esophageal eosinophilia, but the underlying mechanisms promoting eosinophil accumulation remain unclear. David Artis and his colleagues describe a new mouse model of EoE-like disease. The development of EoE-like disease is dependent on thymic stromal lymphopoietin (TSLP) and basophils, whereas inhibition of TSLP or depletion of basophils attenuates established disease. Moreover, individuals with EoE have increased TSLP expression and basophils in the esophagus, suggesting that the TSLP-basophil axis can be targeted in patients with EoE.

Genetic variants at multiple loci of chr5p15.33 have been associated with susceptibility to numerous cancers. Here the authors show that the association of one of these loci may be explained by a variant, rs36115365, influencing telomerase reverse transcriptase (TERT) expression via ZNF148.

A study leveraging transsynaptic tracing demonstrates rapid and extensive integration of human glioblastoma organoids into the mouse brain.

Korobkina et al. show that ACLY in brown fat prevents metabolic overload in the tricarboxylic acid cycle, thus ensuring adequate thermogenesis by avoiding cellular stress.

A comprehensive characterization of the thymic stroma identifies a tuft-cell-like thymic epithelial cell population that is critical for shaping the immune niche in the thymus.

A region on chromosome 19p13 is associated with the risk of developing ovarian and breast cancer. Here, the authors genotyped SNPs in this region in thousands of breast and ovarian cancer patients and identified SNPs associated with three genes, which were analysed with functional studies.

We find that, in mice, although the individual loss of Parkin or OMA1 does not affect mitochondrial integrity, their combined loss results in small body size, low locomotor activity, premature death, mitochondrial abnormalities and innate immune responses.

Paul Pharoah and colleagues report the results of a large genome-wide association study of ovarian cancer. They identify new susceptibility loci for different epithelial ovarian cancer histotypes and use integrated analyses of genes and regulatory features at each locus to predict candidate susceptibility genes, including OBFC1.

This Resource describes data, code and tools developed for the Human Reference Atlas and the Human BioMolecular Atlas Program for building and navigating a multiscale human atlas.

Biologics are delivered by a pill that pricks the stomach wall.

The p53 target FBP1 is elevated in senescent-like metabolic-dysfunction-associated steatohepatitis hepatocytes but suppressed through promoter hypermethylation and proteasomal degradation in most human hepatocellular carcinomas.

The EML4-ALK oncogene forms  cytoplasmic protein condensates that are associated with its oncogenic signaling. Here, the authors demonstrate that these EML4-ALK assemblies also sequester receptor tyrosine kinase (RTK) adapter proteins suppressing signaling which was reversed upon ALK inhibition, resulting in rapid resensitisation to growth factors and tumor cell survival.

Infusion of CD19-directed chimeric antigen receptor T cells into two patients with chronic lymphocytic leukaemia resulted in complete tumour remission and persistence of the infused cells more than ten years later.

The tumor suppressor p53 is the guardian of the genome. Here, the authors use comprehensive approaches to demonstrate that transient p53 activity induces revival stem cells to promote the regeneration of severely irradiated intestinal epithelium in mice.

Katherine Nathanson and colleagues report a genome-wide association study identifying two loci associated with susceptibility to testicular germ cell tumor.

During aging, the ability of skeletal muscle to repair itself declines, in part due to a decrease in muscle stem cells. Here, the authors report that muscle stem cells that accumulate mitochondrial damage fuse with existing muscle fibers in a manner that depends on the induction of Scinderin.

A neural epigenetic signature detectable via plasma analyses is prognostic in patients with glioblastoma, resembling an oligodendrocyte-progenitor- and neuronal-progenitor-cell-like state and showing increased neuro-to-glioma synapse formation.

Oestrogen negative breast cancer is associated with a poor prognosis. In this study, the authors perform a meta-analysis of 11 breast cancer genome-wide association studies and identify four new loci associated with oestrogen negative breast cancer risk. These findings may aid in stratifying patients in the clinic.

Breast cancer risk for BRCA1/BRCA2 mutation carriers varies depending on other genetic factors. Here, the authors perform a case-only genome-wide association study and highlight novel loci associated with breast cancer risk for BRCA1/BRCA2 mutation carriers.

Walsh and colleagues use prospective sequencing in a large cohort of pediatric patients with solid tumors to detect mutations in cancer predisposition genes and guide downstream clinical care.

RMC-7977, a multi-selective RAS(ON) inhibitor, exhibits potent tumour-selective activity in multiple pre-clinical models of pancreatic ductal adenocarcinoma through a combination of pharmacology and oncogene dependence.

Hakon Hakonarson and colleagues report the identification of two new susceptibility loci for inflammatory bowel disease (IBD). One variant is near a gene encoding tumor necrosis factor receptor subfamily member 6B and is associated with increased levels of this protein in serum from individuals with IBD.

Thomas Wiesner and colleagues report that germline mutations in BAP1 predispose to melanocytic tumors ranging histopathologically from epithelioid nevi to atypical melanocytic proliferations. Some BAP1 mutation carriers also developed uveal or cutaneous melanomas.

LKB1 tumour suppressor gene is frequently mutated in lung adenocarcinoma. Here the authors show that in genetically engineered mouse models of lung cancer Lkb1 restoration induces growth arrest and drives neoplastic cells toward a more differentiated and less proliferative alveolar type II cell-like state via C/EBP-mediated reprogramming.

We demonstrate the role of the ligand-gated purinergic ion channel P2RX4 in maintaining mouse plasma cells in their bone marrow niche.

ER⁺ breast cancer patients treated with endocrine therapies often acquire resistance and develop metastasis. In this study, the authors demonstrate that endocrine therapies can promote the self-renewal of CD133^hi/ER^lodrug resistant cells with metastatic potential driven through the IL6-Notch3 axis activation.

Over 170 susceptibility loci have been identified by genome-wide association studies in breast cancer. Here, the authors interrogated the role of risk-associated variants from non-breast tissue, and using expression quantitative trait loci, identify potential target genes of known breast cancer susceptibility variants, as well as 11 regions not previously known to be associated with breast cancer risk.

Concurrent frequency-domain diffuse optical spectroscopy and ultrasound imaging can be used to non-invasively monitor placental oxygen haemodynamics in pregnant women in real time.

Alterations in commensal bacteria are associated with an increased risk of allergic disease. David Artis and his colleagues now report that commensal-derived signals influence basophil development and T_H2 cytokine–dependent allergic airway inflammation by suppressing serum IgE levels. Individuals with hyper IgE syndrome also have elevated circulating basophil numbers, suggesting a mechanistic link between commensal bacteria, B cell–mediated production of IgE and basophil hematopoiesis.

BRCA2 has essential roles in suppressing genome instability at stalled replication forks, but how this is achieved remains unclear. Here, the authors apply Okazaki-fragment sequencing to predict sites of genomic instability caused by head-on transcription-replication conflicts upon BRCA2 loss.

Stig Bojesen, Georgia Chenevix-Trench, Alison Dunning and colleagues report common variants at the TERT-CLPTM1L locus associated with mean telomere length measured in whole blood. They also identify associations at this locus to breast or ovarian cancer susceptibility and report functional studies in breast and ovarian cancer tissue and cell lines.

Sialic acid transporters (SiaT) are required for sialic acid uptake in a number of human pathogens and are of interest as targets for antimicrobial drug development. Here the authors present the substrate bound SiaT structure from the uropathogen Proteus mirabilis and provide insights into the mechanism of sialic acid transport.