Cancer at Nature Portfolio

Zheng et al. identify a role for CD160 in regulating CD8⁺ T cell exhaustion and cytotoxicity through the AKT–NF-κB pathway. The transfer of CD160⁺CD8⁺ T cells overcomes resistance to anti-PD-1 treatment in colorectal cancer models.

Al-Hilal, Chrysovergi et al. identify a role for durotaxis in lung fibrosis and metastatic pancreatic cancer, mediated by the FAK–paxillin mechanosensor complex, and demonstrate therapeutic targeting of this pathway using the small molecule JP-153.

As presented at the 2025 World Conference on Lung Cancer, in a multiarm phase 2 trial, perioperative immunotherapy was safe and feasible in patients with resectable diffuse pleural mesothelioma, with exploratory data suggesting that ctDNA kinetics could be informative of tumor regression and post-treatment survival.

Kaluba, Rogers et al. show that in cancer cells that can metabolize ketones, they may reroute them to produce cytosolic acetyl-CoA and support tumour growth.

Yang, Li, Huang, Ji, Luo, Jiang and colleagues report that chemotherapy induces MLKL PARylation and necroptosis in tumour endothelial cells, which in turn affects tumour-associated macrophages and CD8⁺ T cells, promoting immunosuppression and tumorigenesis.

Yin, Lin, Cai, Nie and colleagues report phase separation of ERCC6L2 as a mechanism that regulates RNF138-mediated ubiquitination and degradation of CtIP, thereby modulating DNA end resection and treatment response to ATM inhibitors in cancer.

In this single-arm phase 2 trial in patients with HR⁺HER2⁻ advanced breast cancer, treatment with the HER3-targeting antibody–drug conjugate paritumab deruxtecan led to encouraging objective response rates, and comprehensive exploratory analyses indicate potential biomarkers of response.

In the secondary endpoint analysis of the phase 3 SONIA trial, circulating tumor DNA (ctDNA) analysis showed that a pretreatment aneuploidy-based high ctDNA level in patients with advanced breast cancer was associated with benefit from first-line treatment with CDK4/6 inhibitors.

The cortex fuels essential physiological processes with glucose-derived carbon, while gliomas fuel their aggressiveness by rerouting glucose carbon pathways and scavenging alternative carbon sources such as environmental amino acids, providing a potential therapeutic target.

A combination of mouse model data and data from a randomized phase 2 trial in patients with breast cancer in remission demonstrates feasibility, safety and a reduction in residual tumor cells following treatment with hydroxychloroquine and/or everolimus.

Shao et al. developed an MRI–pathology-based foundation model to assess the pathology of prostate cancer for diagnosis and grading of tumors. The model is noninvasive and outperforms current pathological assessments.

Fluid shear stress plays a role in medulloblastoma metastasis through a PIEZO2-actomyosin-GLUT1 signalling cascade.

SMARCA4 deficiency is associated with poor prognosis in non-small cell lung cancer (NSCLC). Here the authors report that loss of SMARCA4 in NSCLC cells is associated with resistance to ferroptosis, mediated via inhibition of ALDH16A1 expression and thioredoxin degradation.

Gasnier et al. identify NOX1 and NPY1R as markers of colon stem cells within the mouse caecum and the middle and distal colorectum, respectively. These stem cells contribute to the initiation of invasive colon tumours in mice.

SOX2 is known to be oncogenic in squamous cell carcinomas. Here, the authors demonstrate that SOX2 promotes global histone acetylation and reprograms lipid metabolism in esophageal squamous cell carcinoma cells.

The role of the tumour microenvironment in the response to immune checkpoint inhibitors in metastatic melanoma remains poorly understood. Here, single cell profiling of metastatic melanoma samples identifies associations of the mature dendritic enriched in immunoregulatory molecules subtype with immunotherapy response.

Missense mutations in the twelfth codon of KRAS are key drivers of lung cancer. Here, the authors develop a CRISPR-High Fidelity-Cas9-based strategy to target KRAS-G12C and KRAS-G12D mutants, reducing tumourigenicity without wild type KRAS off-targeting and circumventing certain therapy resistance mechanisms in preclinical models.

The response to immune checkpoint blockade in head and neck cancer has been heterogenous. Here, the authors utilise longitudinal sampling of a head and neck squamous cell carcinoma model to identify biomarkers of response.

The authors identify pre-TCR as a key biomarker and therapeutic target in T-ALL. Targeting it with an anti-pTα antibody–drug conjugate inhibits leukemia-initiating cells and tumor growth in mice, offering promise for relapsed/refractory T-ALL treatment.

The tumour microenvironment often suppresses immune cell function and cancer-associated fibroblasts (CAF) are involved in the process. Here authors show in human tumours and in mouse models that AEBP1 is highly expressed in CAFs, and via autocrine stimulation of its receptor CKAP4, it induces the upregulation of PD-L1, which inhibits the anti-tumor T cell response.

Understanding the mechanisms of chemoresistance in multiple myeloma (MM) remains elusive. Here, the authors identify a long non-coding RNA termed as PLUM that is overexpressed in NF-ĸB mutant high-risk MM and interacts with EZH2 to mediate PRC2 complex formation promoting chemoresistance via the activation of the UPR pathway.

CRAF is one of three RAF-family kinases and is mutated in cancer and RASopathies. Jang et al. report structural and mechanistic studies of CRAF/MEK1/14-3-3 complexes that explain distinct features of CRAF regulation.

The transcription factor ATF6 causes an enrichment in long-chain fatty acids in the colonic epithelium, which leads to changes in the gut microbiota and contributes to the development of colorectal cancer in humans and mice, thereby linking endoplasmic reticulum stress responses to lipid metabolism and tumorigenesis.

Cancer cells can squeeze through confined spaces and undergo nuclear deformation, leading to changes in chromatin organisation. Here, the authors show that mechanical constriction in microcapillaries reprograms melanoma cells to a tumorigenic stem cell-like state through the mechanosensor PIEZO1.

The efficacy of immunotherapies in lung cancer is often restricted by formation of dense and aligned collagen fibers within the tumor microenvironment. Here the authors develop an inhalable lipid nanotherapeutic agent to disrupt collagen fiber alignment and alleviate immunosuppression in lung tumors.

Profiling low-quantity EV-DNA is challenging. Here the authors present TEMPT, a bisulfite-free method for whole-genome methylation analysis from sub-nanogram EV-DNA, which classified gastric cancer and benign cases.

The development of moderate magnetic hyperthermia (MH) for tumor ablation while concurrently restoring bone homeostasis shows potential for osteosarcoma (OS) therapy. Here this group combines magnetothermal nanoparticles with MH temperature-controlled borosilicate bioactive glass achieving OS cell impair while activating TNF signaling pathway for therapeutic purpose.

Cangkrama et al. show that tumor cells from various cancer types use the mitochondrial trafficking protein MIRO2 and nanotubes to transfer mitochondria into surrounding fibroblasts, thereby inducing cancer-associated fibroblast differentiation and subsequent tumor growth.

Lung cancer screening effectiveness can be subject to variation based on personal risk factors. Here the authors report that heterogeneity in lung cancer screening effectiveness is primarily driven by histology.

Human diseases may evolve by migration or spread, but understanding these complex processes is challenging. Here, the authors leverage graph homomorphisms to reconstruct trees describing histories of metastatic migrations and viral host-to-host transmissions.

This study explores the relationship between telomere length and clonal hematopoiesis. Splicing factor and PPM1D gene mutations are more frequent in people with genetically predicted shorter telomere lengths, suggesting that these mutations protect against the consequences of telomere attrition.

Mechanical confinement of cancer cells at the tumour–microenvironment interface induces phenotype switching through chromatin remodelling by HMGB2, leading to a more invasive and drug-resistant state in melanoma.

The role of polyclonal competition in immunotherapy response is poorly understood. Here, the authors perform multiregional sequencing of a metastatic urothelial carcinoma patient that exhibited different treatment responses to anti-PD-1 therapy at each tumour site and identify distinct cancer-related properties.

Neurotoxicity impacting the central and peripheral nervous systems is a considerable adverse effect of both conventional and novel cancer therapies. In this Review, Karschnia et al. outline what is currently known about the mechanisms that underlie the clinical symptoms of central nervous system injury and peripheral neuropathy and the ongoing development of interventions to treat and prevent this unmet medical need.

Targeted radionuclide therapy (TRT) is a therapeutic modality that combines the strengths of radiotherapy and systemic molecularly targeted therapy. Over the past few years, new TRT agents have been developed against an expanding array of molecular targets, particularly in cancers with limited treatment options. The authors of this Review discuss these advances, focusing on what constitutes an optimal target and discussing lessons learned from past experience in order to broaden the scope of TRT.

This Review discusses what comprises the ‘cancer microbiome’, summarizing the studies on tumour-associated microbes, examining the evidence and assessing their impact on the disease.

In this Review, Easwaran and Weeraratna outline how ageing leads to epigenetic alterations in the tissue microenvironment, enhancing clonal expansion of mutations and ultimately increasing cancer risk.

The global incidence of thyroid cancer rose sharply after the 1980s despite stable mortality rates. Chen and Haymart outline known and emerging risk factors for thyroid cancer and discuss strategies to address the public-health issues of thyroid cancer overdiagnosis and overtreatment.

The Radiomics Quality Score (RQS) was developed to assess the rigour of studies using radiomics, a tool for medical imaging analysis. The RQS has been widely used in the field and now needs an update (RQS 2.0) to address contemporary needs. The authors of this Review introduce RQS 2.0, which integrates radiomics readiness levels to provide a structured framework towards clinical implementation.

In this Perspective, de Magalhães explores the evolutionary relationship between cancer and ageing, proposing that the need to minimize cancer risk early in life may contribute to tissue degeneration later on, representing a trade-off that constrains the evolution of longer lifespans.

Allogeneic haematopoietic stem cell transplantation remains the cornerstone of curative treatment for advanced myeloid malignancies. In this Perspective, Foldvari et al. propose that T cells engineered to express tumour-reactive T cell receptors (TCRs) may offer a safer and more effective alternative. They outline key considerations for identifying and validating suitable target antigens and matching TCRs, and for advancing these therapies towards clinical application.

Ubellacker and Dixon summarize the latest discoveries on ferroptosis in cancer, covering the molecular and cellular pathways underlying sensitivity and resistance to this type of cell death, as well as potential translational applications in cancer therapeutics.

In this Review the authors explore the emerging role of HER2 in urothelial carcinoma, highlighting its biological and clinical significance, the challenges of using HER2 as a biomarker, and the variability and complexity of HER2 assessment. Evidence supporting HER2-targeted therapies and future directions for research and clinical applications are also discussed.

Ageing reshapes immune composition, function and regenerative capacity, with profound effects on tumour immunity, cancer progression and treatment outcomes. In this Review, Dolan and colleagues examine how age-resolved immunoprofiling, insights from ageing haematopoiesis and preclinical modelling are uncovering immune ageing dynamics and therapeutic challenges — revealing new opportunities to optimize cancer therapy across diverse age groups.

Immune-checkpoint inhibitors have dramatically improved the outcomes in patients with advanced-stage driver-negative non-small-cell lung cancer (NSCLC), although most patients will ultimately have disease progression on these agents and the most effective treatment approach in this scenario remains uncertain. In this Review, the authors describe the outcomes in patients receiving second-line therapy for advanced-stage NSCLC and provide an overview of emerging therapies and future areas of research in this challenging clinical setting.

Tumour-associated blood vessels are abnormal in structure and function, and this can limit immune cell infiltration into tumours and contribute to the immunosuppressive tumour microenvironment. This Review highlights how tumour angiogenesis impacts antitumour immunity and explains why combining anti-angiogenic strategies with immunotherapies could improve clinical outcomes for patients with cancer.

Park and colleagues propose a conceptual framework in which dysregulation of resident tissue macrophages is both a central contributor to how an aging immune system causes diseases, including cancer, and a potential therapeutic target.

We provide two procedures to cover distinct approaches for the initiation of lymph node metastases in mice: one for studying the metastatic cascade in tumorigenic cells and the other for studying the effect of metastatic formations in the host.

Effective tumour-specific T cell immunity — and the success of cancer immunotherapies — relies on the presentation of antigens via human leukocyte antigen (HLA) molecules. In this Review, Bassani-Sternberg and Huber explore recent advances in understanding the repertoire of tumour-specific antigens, as well as how disruptions in antigen processing and presentation contribute to immune evasion and resistance to immune checkpoint blockade. The authors also highlight how these insights can inform the design of personalized neoantigen-based vaccines and combination therapies aimed at outpacing tumour immunoediting.

Cases of early-onset colorectal cancer (EOCRC) have risen alarmingly since the 1990s, alongside a surge in metabolic diseases, particularly obesity and type 2 diabetes mellitus (T2DM), among young populations. This Review synthesizes evidence regarding the association of obesity and T2DM with EOCRC.

Kim and colleagues provide an overview of the current state of the art of nanomaterials and their application in immuno-oncology, discussing preclinical development and the clinical landscape.

This Review discusses how mechanical cues can influence extracellular vesicle targeting and activity.

This Perspective discusses recent progresses in development of in vitro tumor models and the current challenges in this field.

In this Review, Parida and Malladi summarize the metabolic adaptations of tumour cells upon dissemination to the brain, outline the metabolic crosstalk between cancer and brain-resident cells and discuss potential strategies to target these adaptations to improve outcomes for patients with brain metastasis.

In this Review the authors describe current knowledge on cellular plasticity in the bladder urothelium, emphasizing its role in bladder repair and tumorigenesis, and explore the molecular mechanisms of urothelial plasticity and discuss its potential as a novel therapeutic target for bladder-related diseases.

Next-generation, oral selective oestrogen receptor degraders (SERDs) have been shown to improve outcomes in patients with advanced-stage oestrogen receptor (ER)-positive, HER2-negative breast cancer, particularly those with acquired ESR1 mutations. Now, the proteolysis-targeting chimera (PROTAC) SERD vepdegestrant, which induces ER degradation directly rather than indirectly, has also demonstrated efficacy in this setting, raising questions over the optimal choice and sequencing of treatments.

Despite several decades of research that has revealed roles in the development and progression of many solid tumours, clinical translation of research targeting epithelial–mesenchymal transition (EMT) has thus far been limited. In this Review, the authors provide a summary of the role of EMT in cancer development and progression in the context of this lack of clinical translation, summarize the current status of direct or indirect EMT-modulating agents in clinical development, and highlight the major barriers to the development of EMT-related clinical interventions.

Although immune checkpoint inhibitors can prolong survival in people with clear-cell renal-cell carcinoma, disease progression is frequent. Here, the authors explore potential mechanisms that might drive intrinsic or acquired resistance to immune checkpoint inhibitors in clear-cell renal-cell carcinoma, including malignant cell-intrinsic and immune-cell factors.

Radiotherapy has an established role in the treatment of many patients with cancer, with evidence suggesting that this modality can also have immunostimulatory effects in certain scenarios. More recently, evidence has emerged supporting a role of the microbiome in influencing the incidence and severity of toxicities in patients receiving radiotherapy as well as in mediating possible synergy with other therapeutic interventions, including immunotherapy. In this Review, the authors explore the clinical potential of these emerging relationships.

In this Perspective, Lazure and Gomes argue that metabolic changes that occur as a result of ageing may shape tumour initiation and progression and the development of metastatic disease.

This comprehensive Review describes the biological function of the mismatch repair (MMR) machinery, the genomic sequelae of defects in this machinery and the roles of hereditary or sporadic MMR deficiency in cancer predisposition and/or tumour development. The authors also discuss the clinical implications of MMR deficiency with a specific focus on diagnostic approaches, therapeutic strategies and mechanisms of resistance to immune-checkpoint inhibitors.

In this Review, Henry and DeGregori discuss the contributions of the various models and methods used to study the connection between ageing and cancer, highlighting the strengths and limitations of those models and technologies, as well as advocating for the wider adoption of age-appropriate models of cancer to improve our clinical translation of approaches to prevent and treat human cancers.

Aneuploidy, a defining feature of cancer, is linked to immune evasion and therapeutic resistance. This Perspective reviews approaches to quantify tumor aneuploidy and evaluates its potential as a biomarker for guiding immune checkpoint blockade.

A study now indicates that CD160⁺CD8⁺ T cells in patients with colorectal cancer modulate anti-tumour immune responses and may influence disease progression. Their combination with immune checkpoint blockade therapy has emerged as a promising strategy to enhance therapeutic efficacy and patient outcomes in colorectal cancer.

We assessed the utility of RNA sequencing in molecular diagnostics by analyzing a large pan-cancer cohort ranging in age from infants to seniors. This technique is highly sensitive for the identification of gene alterations that can guide diagnosis and targeted therapy, and enables additional biological and clinical interpretation of findings beyond standard DNA-sequencing protocols.

In a recent study, Salomó Coll et al. demonstrate that impaired ER-phagy in Kras-mutant pancreatic acinar cells leads to the accumulation of protein aggregates and disruption of acinar cell homeostasis, thereby cooperating with oncogenic KRAS to promote cellular transformation.

The pre-T cell receptor is essential for T cell development. It is also an emerging immunotherapy target.

Gene fusions are potent drivers of cancer, and nuclear condensates are known to have a role in transcription. By creating synthetic fusion oncogenes, we show that nuclear condensate formation might be a general feature of fusion oncoprotein-directed transcription, including in brain tumour development.

We developed paclitaxome-2, an optimized version of the sphingomyelin-derived paclitaxel nanovesicle paclitaxome. Leveraging the cationization-enabled transcytosis machinery boosted tumor penetration, and incorporating CD47 ‘self’ peptide masking minimized phagocytosis. Co-delivery of gemcitabine or carboplatin improved therapeutic outcomes in advanced pancreatic cancer and post-surgical triple-negative breast cancer in mouse models.

Luis Diaz describes how a molecular blood assay revealed the tiniest traces of DNA from a tumor, changing how we monitor cancer.

Glioblastoma, an aggressive brain cancer, depends on the amino acid serine as a fuel source. A serine-deficient diet has been shown to slow tumour growth in mice.

According to the ‘grow or go’ model, cancer cells can switch between invasive and proliferative states. A zebrafish model of skin cancer shows that the invasive switch is triggered by mechanical compression of the cancer cells by surrounding tissues. In this way, the physical environment can reprogramme the cell to dictate cancer behaviour.

Some glioblastomas steal serine from their environment — a weakness that opens the door to treatment.

Prostate MRI has emerged as a way to improve accuracy in prostate cancer diagnostics. However, the subjectivity of assessments remains a challenge. New research shows that AI can help in this task and serve as a tool to improve MRI-based prediction of prostate cancer aggressiveness.

Cancer-associated fibroblasts represent a functionally diverse and heterogeneous entity within the solid tumor microenvironment. Mitochondrial transfer from cancer cells to fibroblasts is now shown to act as a reprogramming stimulus, driving metabolic and functional differentiation of fibroblasts to support tumor growth.

The landmark CHALLENGE trial has revealed that a 3-year structured, behaviourally supported exercise intervention substantially improves both disease-free and overall survival in patients with resected phase II–III colon cancer, marking a genuine paradigm shift in survivorship care. By demonstrating modification of the course of disease rather than merely symptom alleviation, these results elevate exercise from ancillary support to evidence-based therapy and should compel oncology teams to embed expert-guided exercise into routine care.

Genomic sequencing promises targeted treatment for every patient with cancer; the reality is much tougher to deliver.

Lactic acid activates the MondoA–TXNIP pathway, dampening CD8⁺ T cell responses and boosting regulatory T cell function. Inhibiting MondoA revives antitumour immunity and amplifies the effects of anti-PD-1 treatment.

In this Comment, Boyi Gan discusses disulfidptosis, a newly identified, redox-driven cell death pathway triggered by disulfide stress, and highlights its therapeutic potential while underscoring gaps in mechanistic understanding and key challenges for future research.

Chia, Johnson et al. outline a mechanism for how pulmonary viral infections can awaken dormant disseminated cancer cells to enhance metastatic burden.

Previous investigations of the genome of Wilms tumour have demonstrated surprisingly few driver mutations and low tumour mutational burden. Integrating duplex sequencing and use of laser-captured specimens and tumour organoids unveiled a fourfold increased tumour mutational burden and a new vision of clonal architecture in infant Wilms tumour.

A vast landscape of ‘undruggable’ cancer targets remains beyond the reach of conventional therapeutic agents. Recent advances in artificial intelligence (AI), however, are challenging this paradigm. Synthesizing insights from a Cancer Moonshot workshop, we argue that systemically addressing the undruggable target space with AI requires a new conceptual framework. We highlight the failure of current target taxonomies and the need for benchmarking datasets, and re-evaluate clinical validation for novel AI-driven modalities.

Most studies on how exercise affects the survival of people with cancer have been observational. A clinical trial provides compelling evidence of the benefits of physical activity.

A pair of phase 1 trials evaluating antibody–drug conjugates identify potential strategies to treat advanced gastroesophageal cancers and highlight the rapid expansion of claudin18.2-targeting drug development in solid tumors.

Recent extreme weather events have impacted communities once considered safe from climate hazards, posing growing challenges to cancer control efforts. Here, Nogueira and Salas argue that the oncology community urgently needs to prioritize solution-focused adaptation and mitigation actions.

Immunomodulation in draining lymph nodes can be studied in a mouse model of metastasis.

Advances in molecular profiling technologies that capture both genotype and phenotype, coupled with an improved understanding of the biological mechanisms underlying prostate cancer progression, set new molecular biomarkers for advancement into the clinic to improve prognostication, therapy selection and disease monitoring for patients with prostate cancer.

Cereblon-based molecular glue degraders provide a powerful strategy to target previously intractable proteins. This approach has now enabled selective elimination of a metabolically essential zinc finger transcription factor that drives resistance to KRAS inhibition in pancreatic cancer.

Lyons et al. explored the rules of specificity and function for condensates formed by oncogenic fusion proteins, and identified a common molecular signature in these oncoproteins that compartmentalizes RNA polymerase II to confer an increase in gene activation and consequent cancer phenotypes.

The SERENA-6 trial assessed a paradigm-shifting approach to personalized cancer therapy in patients with advanced-stage breast cancer, in which therapy was switched upon the identification of resistance-related mutations in ESR1 in circulating tumour DNA (ctDNA). Herein, we discuss how the results of this trial challenge the standard-of-care management for these patients, in whom therapy changes are otherwise undertaken only after radiographic and/or clinical progression.

In a recent study published in Nature, Liu, Wang, et al. investigate the mechanisms underlying cytarabine-induced neurotoxicity and provide a mechanistic explanation for the differing neurotoxicity profiles of other nucleoside analogues, such as gemcitabine.

A chimeric antigen receptor (CAR)-natural killer (NK) cell therapy shows promise in a patient with severe systemic sclerosis and offers a scalable, off-the-shelf developmental approach.

DNA segments that are naturally excised during immune-cell development can replicate, drive damage at various genomic sites and lead to cancer recurrence.

Exercise promotes changes in the gut microbiota that enhance anti-tumour T cell responses.

The authors present a protocol for the self-assembly of single-cell suspensions into spheroids by the liquid overlay method, followed by a modular framework of orthogonal assays to phenotype spheroids both longitudinally and at an endpoint.

A comprehensive protocol for designing and performing magnetic resonance fingerprinting from chemical exchange saturation transfer and semi-solid magnetization transfer imaging using artificial intelligence to extrapolate information from proteins, metabolites and pH.

Mass spectrometry-based proteomic studies involve tissue lysis. Herein, we updated our 2018 protocol¹ by implementing a sonication step into urea-based tissue lysis to improve the detection of membrane-bound and DNA-binding proteins.

Behavior-guided transcriptomics is an extension to the BEHAV3D protocol, for the integration of T cell live-imaging data with single-cell transcriptomics, enabling analysis of gene programs linked to dynamic T cell behaviors.

Establishment and robust expansion of human fetal brain organoids, their characterization and adaptation for downstream analyses, and how to genome engineer them to generate bottom-up brain tumor models.

We present a practical workflow for end-to-end weakly supervised deep learning to predict biomarkers directly from whole-slide images, enabling clinical researchers to work with engineers to set up a complete computational pathology project.

The authors introduce MACHETE (molecular alteration of chromosomes with engineered tandem elements), a clustered regularly interspaced short palindromic repeats directed Cas9-based system for the efficient deletion of megabase-sized genomic regions.

CONIPHER is a computational framework for accurately inferring subclonal structure and the phylogenetic tree from multisample tumor sequencing, accounting for both copy number alterations and mutation errors.

This protocol presents a computational approach to scoring drug sensitivity that integrates multiple dose–response parameters into a single response metric and identifies differences in drug-response patterns between cancer cells and healthy control cells.

Invasion–adhesion-directed expression sequencing adapts the 10x Genomics 5��� single-cell RNA sequencing protocol to enable generation of bacterial and eukaryotic DNA libraries to identify adherent or invasive bacteria and the associated host transcriptome at a single-cell level.

The authors present a protocol for genome-wide clustered regularly interspaced short palindromic repeat screening of three-dimensional neurospheres.

The current serum tumour markers α-fetoprotein, human chorionic gonadotrophin, and lactate dehydrogenase show limited value for testicular cancer relapse detection. A recent study highlights that false-positive elevations in follow-up monitoring are common and, conversely, many patients do not have elevations despite proven relapse. These findings highlight the potential for circulating microRNAs to be used as improved biomarkers for relapse detection.

A newly composed single-cell transcriptomic atlas of tumor-infiltrating T cells across 16 cancer types revealed previously undescribed T cell states and heterogeneity. A unique T cell stress response state, T_STR, was linked to immunotherapy resistance. Our high-resolution T cell reference maps, web portal, and annotation tool can assist efforts to develop T cell therapies.

Therapeutic products containing CD8⁺ and CD4⁺ T cells expressing CARs are effective at inducing remission in patients with cancer. How CD4⁺ CAR T cells contribute to the anti-tumor response has not been well established. A study uses syngeneic models and in vivo imaging to glean mechanistic insights into how CD4⁺ T cells target tumors.

Antigen presentation is fundamental to anti-tumor immunity, but our understanding of the physiological and molecular inputs to the process in different contexts remains limited. Two new studies explore the contribution of cell-intrinsic proteolytic mechanisms and cell-extrinsic hot and cold tumor microenvironments in shaping the antigenic landscape in lung cancer.

A preprint by Lad et al. shows that tumour-associated neutrophils in glioblastoma originate from skull bone marrow and acquire an antigen-presenting cell phenotype intratumorally in the presence of local T cells.

In this study, Insco et al. find patient-specific CDK13 mutations to impede RNA surveillance, leading to the accumulation and translation of prematurely terminated RNAs that drive malignancy in melanoma models.

An article in Nature Biomedical Engineering reports a simple and hardware-independent peptide-mediated delivery method for the CRISPR-mediated engineering of T cells.