Gene expression-based molecular subtypes in glioblastoma from The Cancer Genome Atlas Network (TCGA-GBM) unraveled the pathological origins by identifying tumour cell driver genes. However, the causal inference between molecular subtype origins and their therapeutic efficacy remains obscure.

Acute myeloid leukaemia (AML) remains the most common type of leukaemia in adults. Despite advances in conventional therapies, high relapse rates persist, underscoring the need for novel approaches such as chimeric antigen receptor T (CAR-T) cell therapy. C-type lectin-like molecule-1 (CLL1)-targeted CAR-T emerges as a promising treatment for relapsed/refractory (R/R) AML. Although approximately 70% patients achieved remission, only a subset achieved minimal residual disease-negative remission, which still has much room for improvement. The main reasons for the failure of CLL1 CAR-T-cell therapy include: (1) persistence of CLL1-negative AML cells persist due to antigen escape; (2) downregulation of interleukin (IL)-12 and other cytokines by the immunosuppressive tumour microenvironment (TME), contributing to the exhaustion of both endogenous T cells and CLL1 CAR-T cells. We synthesise a combination of CAR-engineered dendritic cells (CAR-DCs) and CLL1 CAR-T cells to overcome current limitations. CAR-DCs enhance antigen cross-presentation to activate endogenous T cells against antigen-negative clones, secrete immunostimulatory cytokines (e.g., IL-12) to sustain CAR-T activity, and remodel the TME. Key challenges involve optimising CAR designs (e.g., incorporating Fms-like tyrosine kinase 3 ligand [FLT-3L] or CD40 signalling domains), mitigating toxicity and establishing clinical administration protocols. In this review, a focused discussion was provided on the specific challenges limiting CLL1-targeted CAR-T-cell therapy in R/R AML, namely antigen escape and the TME, and a novel combination strategy of CAR-DCs with CLL1 CAR-T cells was proposed as a promising approach to mitigate these barriers. Here, the rationale, current research advances, and future perspectives of this synergistic strategy were critically examined. HIGHLIGHTS: Our earlier clinical trials showed that C-type lectin-like molecule-1 (CLL1)-targeted therapy for refractory/relapse acute myeloid leukaemia (AML) was validated, which still has a considerable room for improvement. We summarise the clinical trials and basic research on the dendritic cell (DC) therapy and chimeric antigen receptor-engineered DC (CAR-DC) therapy. We explored the synergistic mechanism and prospects of CLL1 CAR-DC cells combined with CLL1 CAR-T cells in AML.

Although the contribution of matrix stiffness to aggravating the malignant features of HCC cells has been well documented, the effects of matrix stiffness on chemoradiotherapy resistance and its underlying mechanism remain largely elusive.

Precision medicine has evolved through distinct phases, from the origins of the Human Genome Project to mutation-based targeted therapies. This editorial posits that "stereological cell biomedicine" could be a new approach promoting the development of the next generation of precision medicine. This emerging discipline transitions the focus from genomic data to the multi-dimensional and spatiotemporal complexity of single cells. Driven by advances in Stereo single-cell multi-omics (Stereo Cell-seq), spatial transcriptomics (Stereo-seq), and single-cell surfaceomics (sc-surfaceome), this approach aims to capture the stereologically dynamic interactions between organelles within a cell and between cells in the tissue. We argue that understanding the spatiotemporal location of molecules, particularly protein interactions at organelle interfaces and on the cell surface, is as critical as their abundance for defining cellular function in health and disease. Integrating these high-resolution measurements with artificial intelligence and computational modelling will bridge the gap between advanced omics and pathology. Initiatives such as the newly established European Stereo Cell Center (ESCC) signal a global shift towards this new paradigm, which promises to unlock novel diagnostic biomarkers and therapeutic targets for truly multi-factorial and dynamic precision medicine.

Testicular macrophages (TMs) are key regulators of testicular immune privilege and endocrine function in the testis. However, their age-related heterogeneity and role in testicular degeneration remain poorly characterized.

Metastatic head and neck squamous cell carcinoma (mHNSCC) poses a significant threat to patient survival. Previous studies have identified cathepsin L (CTSL) as a key driver of tumourigenesis, metastasis and chemoresistance. However, the regulatory mechanisms underlying CTSL expression remain poorly understood.

The immune microenvironment of the three most common gynaecological malignancies-tubo-ovarian cancer, endometrial cancer and cervical cancer-has not been systematically studied, limiting clinical application.

The cyclic GMP-AMP synthase (cGAS)-stimulator of interferon (IFN) genes (STING) pathway emerges as a dual-functional role in urologic malignancies, exhibiting context-dependent tumor-suppressive and pro-tumorigenic activities. When this pathway is activated in urologic tumors, IFN transcription and CD8 T cell infiltration are triggered, which has an anticancer effect. However, this pathway facilitates the development of prostate cancer through the up-regulation of regulatory B cells. STING palmitoylation triggers immune escape in renal cell carcinoma, and the STING/SLC14A1 axis also mediates chemoresistance in bladder cancer.

Primary hyperoxaluria type 1 (PH1) is a rare autosomal recessive disorder caused by AGXT mutations, leading to hepatic oxalate overproduction, nephrolithiasis, and progressive renal failure. This study aims to evaluate the therapeutic potential of base editors delivered via lipid nanoparticles (LNPs) for treating PH1.

RNA methylation has emerged as a pivotal layer of post-transcriptional regulation that shapes the biological behavior of cancer cells. Among the diverse chemical modifications identified-such as N6-methyladenosine (m6A), N1-methyladenosine (m1A), 5-methylcytosine (m5C), 7-methylguanosine (m7G), 5-hydroxymethylcytosine (5hmC), and 2'-O-dimethyladenosine (m6Am)-the m7G modification has recently garnered increasing attention. Mounting evidence indicates that m7G methylation plays an essential role in RNA metabolism and profoundly influences cancer initiation and progression.

We previously conducted a comprehensive survey of energy metabolism in osteoarthritis (OA), revealing significant reductions of nicotinamide adenine dinucleotide (NAD) levels in OA cartilage. This study aimed to test whether NAD deficiency present in OA plays a mechanistic role in disease development.

Despite guideline-directed therapies, most patients with advanced oesophageal squamous cell carcinoma (ESCC) derive limited benefit and are unable to tolerate iterative treatment modifications. Therefore, timely identification of resistant cases and the provision of alternative therapeutic options are urgently needed.

Lactylation, a post-translational alteration facilitated by lactic acidderived lactyl-CoA, has emerged as an epigenetic regulator that alters gene expression in macrophages. Emerging data situates lactylation at the nexus of metabolic flux and immune cell destiny, especially in tumor and inflammatory microenvironments.

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