Bacteria-mediated cancer therapy leverages bacteria to modulate the tumor immune microenvironment and deliver therapeutics. However, its clinical application is limited by toxicity, off-target effects, and uncontrolled drug release. Improving tumor targeting and precise payload delivery through rational bacterial engineering is essential for increasing efficacy and safety.

An attenuated Salmonella ΔhtrA::luxI-VNP20009 strain expressing OmpA-SpyTag (AISI-ST) was constructed for the modular surface conjugation of SpyCatcherΔ (SC)-fused quadruple arginine-glycine-aspartic acid (RGD) peptides (named AISI-ST/SC-RGD×4) and for building biointerfaces for enhanced tumor adhesion via RGD-mediated integrin αvβ3 interactions. The tumor-bearing mice received intravenous injections of AISI-ST/SC-RGD×4, and their biodistribution was analyzed using bioluminescence imaging and colony-forming unit (CFU) counts. Quorum-sensing (QS)-regulated high-temperature requirement A (HtrA) and anti-programmed cell death protein 1 (anti-PD1) nanobody expression based on the LuxI promoter in strains was validated by Western blotting. Immune responses were assessed using flow cytometry.

The incubation of the fused proteins with the AISI-ST strain for 1 h was sufficient to form a stable biological interface. The quadruple RGD-modified bacteria (AISI-ST/SC-RGD×4) exhibited greater enrichment in various solid tumors and lung metastases with reduced off-target accumulation. QS induced the expression of the HtrA protein within tumors, resulting in enhanced extracellular polysaccharide-mediated immunogenicity to activate immune cells. Further expression of anti-PD1 nanobodies synergistically enhanced antitumor immunity, increasing the percentage of M1 macrophages (MACS) and CD8⁺ T cell proliferation while suppressing M2 MACS and regulatory T cells (Tregs). This approach achieves potent tumor suppression via targeted immune remodeling.

This study presents octopus-inspired engineered bacteria with a "plug-and-display" system and tumor-specific drug delivery that achieves enhanced tumor targeting and potent antitumor effects. This study describes a promising strategy for the precise and safe clinical translation of bacteria-mediated cancer immunotherapy.

Advanced gastric cancer (AGC) exhibits a high incidence in Northwest China, largely attributed to region-specific dietary patterns and environmental exposures. Its pathogenesis involves complex host-microbiota crosstalk, which has not yet been comprehensively elucidated through integrated multi-omics approaches. Herein, we employed trasncriptomic and shotgun metagenomic sequencing on paired tumoral and peritumoal mucosal tissues from 88 AGC patients in Northwest China. Our aim was to systematically characterize host gene expression profiles, the composition and functional potential of the gastric mucosal microbiota, and their intricate interrelationships.

Transcriptomic profiling clearly distinguished tumoral from peritumoral regions (PERMANOVA, R² = 0.24, P = 0.0001), with 8870 differentially expressed genes (DEGs) identified between the two tissue types. Tumor tissues harbored 8377 up-regulated DEG, which were enriched in extracellular matrix (ECM) organization, cell cycle regulation, signaling transduction, and inflammatory pathways (e.g., PI3K-Akt, IL-17 signaling). In contrast, peritumoral tissues showed 493 up-regulated DEGs primarily associated with metabolic processes. Host gene expression was significantly modulated by Lauren classification in tumoral mucosa (P = 0.025) and by Helicobacter pylori (Hp) infection in peritumoral tissues (P = 0.0424). Hp-infected tissues exhibited 65 up-regulated DEGs linked to transcriptional misregulation in cancer, inflammation, immune activation and mitochondrial pathways. Lauren subtypes displayed distinct transcriptomic signatures: intestinal-type AGC was enriched in metabolic processes, diffuse-type in immune and signal transduction pathways, and mixed-type in Ras/MAPK/ErbB and NF-κB signaling pathways. Correlation analysis between the 8870 DEGs and seven differentially abundant bacterial species (e.g., Serratia surfactantfaciens, Pseudomonas protegens, Prevotella jejuni, and Streptococcus infantis) revealed 13199 significant correlations. Among these, S. surfactantfaciens and P. protegens exhibited the strongest connectivity with host genes. Functionally, the correlated DEGs were involved in ECM structure, cell cycle progression, immune and inflammatory responses, cellular proliferation and differentiation, and metabolic processes.

Our findings demonstrated phenotype- and tissue-specific regulation of host gene expression in AGC and revealed extensive host-microbe interactions. This work fills a critical gap in multi-omics research on AGC in the Northwest Chinese population and suggests potential diagnostic and therapeutic targets for AGC.

Translating high-resolution multiomics data into clinically actionable biomarkers is critical for overcoming therapeutic resistance and tumor heterogeneity in prostate adenocarcinoma (PRAD). To decode the complex immunosuppressive tumor microenvironment (TME) and identify robust prognostic targets, we developed a systematic biomarker discovery pipeline integrating single-cell RNA sequencing (scRNA-seq) mapping and high-dimensional network analysis. By deconvoluting scRNA-seq profiles from over 35,000 PRAD cells, nonnegative matrix factorization (NMF) of the malignant epithelial compartment revealed nine distinct transcriptional metaprograms (MPs). High-dimensional weighted gene coexpression network analysis (hdWGCNA) pinpointed PRAD-MP7 as the core proliferative engine and nominated the malignant-specific gene YBX1 as the master prognostic hub. To establish clinical utility evidence, we validated YBX1 across six independent global PRAD cohorts, where its overexpression robustly predicted poor overall survival (OS) and relapse-free survival (RFS). In vitro functional validation via siRNA-mediated knockdown in DU-145 and PC-3 cells significantly attenuated proliferative and invasive capacities, impairing cell viability and downregulating key progression markers (Ki-67, MMP2, and MMP9). Crucially, immunogenomic profiling mapped YBX1 expression to an "immune-excluded" TME, characterized by depleted CD8+ T cell and dendritic cell infiltration alongside elevated immune checkpoint networks. Serving as a bridge to clinical translation, YBX1 effectively predicted clinical responses in three immunotherapy cohorts and demonstrated broad resistance to 12 chemotherapeutic and targeted agents. Our multiomics integration pipeline highlights YBX1 as a dual-functional oncogene that couples malignant proliferation with immune evasion, establishing it as a highly translational biomarker and an actionable target for precision PRAD management.

To develop a personalized neoantigen therapy strategy for microsatellite stability (MSS)-advanced colorectal cancer (CRC), neoantigens from collected human CRC samples were screened, and the feasibility and effectiveness of these neoantigens in treating CRC were explored. Whole-exome sequencing and transcriptome sequencing were performed to identify somatic mutations, RNA expression, and human leukocyte antigen alleles. Based on these data, neoantigen candidates were predicted, and their immunogenicity was evaluated. Selected neoantigens from patients elicited enhanced T-cell responses in CRC peripheral blood lymphocytes. Mutated peptides SOX9-V144M, ZNF169-A275S, CDH4-V456M, NIM1K-T66M, and MAP3K9-R1008Q were more effective than nonmutated ones in Patient 1. Vaccination with mutant peptides ZNF169-A275S and CDH4-V456M inhibited tumor growth in an autologous humanized CRC mouse model. Highly immunogenic neoantigens are strong candidates for personalized cancer therapy, showing promise for translating into effective treatments for CRC patients with advanced disease.

Glioblastoma (GBM) heterogeneity limits the efficacy of EGFR-targeted therapies. Here, we present a spatially stratified single-cell atlas of IDH-wildtype GBM to dissect the impact of EGFR amplification on tumor architecture. We demonstrate that EGFR amplification disrupts the spatial coupling between evolutionary state and anatomical location, resulting in premature acquisition of invasive phenotypes-a phenomenon we term "accelerated evolutionary velocity." Unlike nonamplified tumors which maintain a strict "Core-to-Margin" developmental gradient, malignant cells in EGFR-amplified tumors acquire invasive mesenchymal traits preemptively regardless of their spatial niche. This accelerated evolution parallels the Core behaving as a "genotoxic stress reservoir" characterized by elevated chromosomal instability (CIN) (p < 2.2 × 10^-16). This genotoxic stress coincides with the emergence of a localized tumor-myeloid axis and an immune-suppressive niche. Using the PriorityScore2 framework, we prioritized Periostin (POSTN) as a top-tier clinically relevant candidate. In the high-CIN environment of EGFR-amplified GBM, in silico network perturbation suggested that POSTN may function as a candidate modulator of mitotic fidelity, potentially buffering against lethal genomic instability while sustaining rapid clonal evolution. Validated across multicenter cohorts, POSTN showed robust upregulation, strong diagnostic performance (AUC = 0.961), and significant prognostic relevance, emerging as a potential therapeutic vulnerability linking accelerated evolution with immune privilege in the GBM ecosystem.

Nucleotide metabolism significantly influences tumor cell proliferation, yet its specific profile in pancreatic cancer remains inadequately understood. This study was aimed at characterizing the nucleotide metabolic profile in pancreatic cancer and assessing the contribution of the key gene adenylate kinase (AK) 4. Multiomics data, including transcriptomic, single-cell sequencing, spatial transcriptomic, and metabolomics datasets, were obtained from publicly accessible platforms. The impact of AK4, a key gene of nucleotide metabolism, on the proliferation and migration of pancreatic cancer cells was investigated using various molecular biological techniques. Nucleotide pathway-related metabolites exhibited marked differences in abundance between pancreatic cancer tissues and normal pancreatic tissues. Single-cell sequencing analysis identified MKI67⁺ and myeloid cells as subsets with overactive nucleotide metabolism. Immune cells from tumor tissues had a higher score of nucleotide metabolism than those from the normal pancreas. Spatial transcriptomics revealed spatial features of nucleotide metabolism in pancreatic cancer. Pancreatic cancer patients displayed distinct clinical heterogeneity in nucleotide metabolism, with elevated nucleotide signaling correlating with poorer patient prognosis. Furthermore, tumor subtypes showed variations in immune microenvironment features and immune checkpoint expression, which may explain their differential prognoses. A nucleotide metabolic-derived prognostic panel had the potential to predict the clinical outcomes of patients with pancreatic cancer. The AK4 gene played a central role in nucleotide metabolism, and its overexpression in clinical pancreatic cancer samples was frequently linked to adverse patient outcomes. Cell-based experiments revealed that AK4 knockdown suppressed pancreatic cancer cell proliferation and migration. Abnormal nucleotide metabolism pathways are implicated in pancreatic cancer onset and progression.

Molecular pathology has, without a doubt, transformed the field of blood cancer. Thanks to pioneers such as Sanger and Mullis, techniques such as next- and third-generation sequencing, and whole exome sequencing have, alongside a revolution in bioinformatics, determined abnormalities in chromosomes and genes with exquisite sensitivity and specificity. These have contributed considerably not just to our understanding of the cell biology, aetiology, classification, and pathophysiology of blood cancer, but also to its diagnosis and management. Good examples of this include the ability to recognise and treat cases of aberrant tyrosine kinase activity with targeted inhibitors and the recognition that certain abnormalities are linked to a more severe outcome, so that focused treatment can begin. This review catalogues these discoveries and describes how they contribute to our understanding of, and thus the treatment of, lymphoma, leukaemia, myeloma, and other myeloproliferative, erythroid, megakaryocytic, and lymphoid neoplasms. Inevitably, as new techniques are developed, we can expect further advances in biomedical science in all aspects of blood cancer.

Isolated adrenocorticotropic hormone (ACTH) deficiency (IAD) is an uncommon endocrine disorder characterised by the selective reduction or absence of pituitary ACTH secretion, resulting in secondary adrenal insufficiency while other pituitary hormone axes remain functional. The clinical manifestations of this condition are frequently non-specific, and may include symptoms such as fatigue, decreased appetite, weight loss, hypotension, and hyponatremia. These symptoms can be easily confused with those of other diseases, resulting in either missed diagnoses or misdiagnoses. Glucocorticoid replacement therapy is generally considered to provide effective symptom relief and a favourable prognosis. In recent years, the widespread use of immune checkpoint inhibitors (ICIs) in cancer treatment has resulted in a significant increase in immune-related adverse events (irAEs). Isolated ACTH deficiency has been reported as a rare yet severe endocrine-type irAE, potentially arising from immune-mediated pituitary injury. In view of the nonspecific nature of its clinical presentation, early recognition and timely intervention are of critical importance.

The present study reports the case of a patient diagnosed with gastric adenocarcinoma who underwent laparoscopic total gastrectomy, followed by combination therapy with oxaliplatin (OXA), nivolumab, and trastuzumab. Approximately eight months into the treatment regimen, the patient exhibited symptoms of isolated ACTH deficiency and hypothyroidism, indicative of a multi-endocrine system adverse reaction. Such multi-system endocrine dysfunction following this combination therapy is relatively uncommon. The present study analyses the patient's clinical presentation, laboratory findings, and imaging data, and discusses the differential diagnosis from post-gastrectomy dumping syndrome.

This case demonstrates that in patients with malignant tumours receiving nivolumab and trastuzumab therapy, the presence of unexplained hypoglycaemia, persistent fatigue, anorexia, nausea, or vomiting - non-specific symptoms - should raise high suspicion for immune-related endocrine adverse reactions. It is imperative to emphasise the significance of preliminary testing for serum cortisol, ACTH, and thyroid function levels. Early recognition and prompt initiation of hormone replacement therapy can effectively prevent misdiagnosis, missed diagnosis, and delayed treatment.

Chondrogenic tumors of the head and neck are exceptionally rare and pose significant diagnostic challenges due to their clinical and radiologic resemblance to more common sellar and spinal lesions. We report two unusual cases: a chondromyxoid fibroma involving the sellar region in a 32-year-old man presenting with diplopia and headache, and a cervical spine chondrosarcoma in a 42-year-old man presenting with progressive quadriparesis. Magnetic resonance imaging in the first case revealed a well-circumscribed extra-axial sellar mass that was completely excised, with histopathology demonstrating lobulated stellate-to-spindle cells in a chondromyxoid stroma and immunonegativity for EMA, GFAP, and Brachyury, confirming chondromyxoid fibroma. The second case showed an expansile C2 vertebral lesion with infiltrative chondrogenic histology, binucleated chondrocytes, and strong D2-40 positivity with SATB2 and Brachyury negativity, consistent with Grade II chondrosarcoma. While the chondromyxoid fibroma patient remains disease-free at 24-month follow-up, the chondrosarcoma patient experienced rapid progression and succumbed within eight months postoperatively. These cases highlight the critical role of integrating radiologic features, histomorphology, and targeted immunohistochemistry in distinguishing benign from malignant chondroid tumors at anatomically complex sites, enabling appropriate management and prognostication.

Cancer cachexia (CC) is a complex pathological condition associated with cancer progression and poor prognosis, particularly in gastrointestinal cancers, and is closely linked to the gut microbiota. Lipolysis in CC may play a key role in driving cachexia progression. However, the role of the gut microbiota in CC-induced lipolysis and the underlying mechanisms remains unclear. In this study, we found that significant gut microbiota dysbiosis in pancreatic cancer cachexia, characterized by diminished abundance of Eubacterium rectale (E.rectale), was negatively associated with lipolysis severity. Furthermore, we demonstrated for the first time that E. rectale derived extracellular vesicles (EVs) can ameliorate lipolysis across multiple CC models. Mechanistically, these effects are mediated by modulating pro-inflammatory macrophages through inhibition of NF-kB signalling, reducing macrophage polarization and inflammatory cytokine secretion. Our findings indicated E. rectale EVs could offer potential therapeutic benefits for CC and emphasize the importance of host-microbiota interactions. Trial Registration: This study was registered at ClinicalTrials.gov (NCT06378853).