MedComm最新文献

Cancer immunotherapy has emerged as a transformative therapeutic strategy that harnesses the immune system to combat malignant tumors, overcoming critical limitations such as the nonspecific cytotoxicity of conventional chemotherapy and radiotherapy and drug resistance arising from target mutations in targeted therapies. Growing evidence demonstrates that the human microbiome plays a pivotal role in modulating immune responses and influencing the efficacy of immunotherapeutic interventions. Although the impact is increasingly recognized, the molecular mechanisms and translational potential of microbiome-based strategies remain incompletely explored. This review systematically elucidates how microorganisms from distinct anatomical sites (including bacteria, fungi, and viruses residing in the gut, oral cavity, skin, respiratory tract, and urogenital tract) and intratumoral microbes modulate the tumor immune microenvironment through metabolites, immune cell priming, and antigen mimicry. Furthermore, we discuss how specific microbial signatures predict responses to immune checkpoint inhibitors (ICIs) and CAR-T cell therapy, and highlight emerging interventional strategies, including fecal microbiome transplantation (FMT), probiotics, and engineered bacteria, that demonstrate synergistic effects with immunotherapy in preclinical and clinical settings. By integrating mechanistic insights with translational advances, this review provides a comprehensive scientific foundation for microbiome-based precision immunotherapy, aimed at improving patient survival outcomes and reducing treatment-related adverse events.

The interplay between diet, gut microbiota, and depressive symptoms is increasingly recognized, but underlying mechanisms remain unclear. We investigated whether adherence to several dietary patterns relates to gut microbial signatures and whether these profiles are associated with depressive symptoms in an elderly Mediterranean cohort. In 644 participants, 16S ribosomal RNA gene sequencing and dietary intake from a food-frequency questionnaire were obtained at baseline and 1-year follow-up. Adherence scores were computed for the Mediterranean diet adherence score (MEDAS), energy-reduced MEDAS (erMEDAS), Dietary Approaches to Stop Hypertension (DASH), Healthy Plant-Based Diet Index (HPDI), Unhealthy Plant-Based Diet Index (UPDI), and Western Diet Score (WESTDIET). Healthy patterns (erMEDAS, MEDAS, DASH, HPDI) were associated with 22, 28, 24, and 16 genera, of which 82%, 75%, 79%, and 88% showed a protective profile (more abundant with lower, or less abundant with higher, depressive symptoms). UPDI and WESTDIET were associated with 20 and 27 genera, but only 25% and 26% were protective. Mediation analyses indicated that gut microbiota mediated the associations of MEDAS (ACME = –0.066, p = 0.006) and erMEDAS (ACME = –0.029, p = 0.011) with depressive symptoms. This study is among the first to test whether diet shapes a microbiota signature that mediates the diet–depression relationship, adding mechanistic insight into diet–mental health research.

This study aimed to evaluate the efficacy and safety of triple human epidermal growth factor receptor 2 (HER2) blockade with trastuzumab, pertuzumab, and pyrotinib (TPPy) versus dual HER2 blockade with trastuzumab and pertuzumab (TP) in the neoadjuvant treatment of HER2-positive breast cancer. Patients with stage II–III HER2-positive breast cancer were randomized (1:1) to receive TPPy or TP alongside weekly nab-paclitaxel for 12 weeks. The primary endpoint was total pathological complete response (tpCR; ypT0/isN0). Exploratory biomarker and pathway analysis was done to identify patients benefiting from pyrotinib. A total of 109 patients were enrolled, and 108 received treatment: 55 in the TPPy group and 53 in the TP group. The tpCR rate was 65.5% (95% confidence interval [CI]: 51.4%–77.8%) in the TPPy group, and 60.4% (95% CI: 46.0%–73.5%) in the TP group (p = 0.585). In the TPPy group, 52 (94.5%) and 23 (41.8%) patients experienced dose interruption and discontinuation, respectively. The most common grade ≥3 adverse events in the TPPy and TP groups were diarrhea (58.1% vs. 0%) and neutropenia (23.6% vs. 15.1%). In conclusion, triple HER2 blockade did not improve tpCR rates compared with dual blockade but was associated with greater toxicity, particularly diarrhea.

Cancer neuroscience has emerged as a transformative frontier in oncology research, focusing on the interplay between cancer cells and the nervous system. Cancer cells establish tumorspecific neural networks within tumor tissues via neurotrophic hijacking. The nervous system regulates tumor initiation, progression, and metastasis either directly by regulating signal transduction in tumor cells or indirectly by modulating the tumor microenvironment (TME). The positive feedback loop between cancer cells and nerves promotes tumor progression. Deciphering the regulatory role of nerves in tumor progression may yield novel anticancer therapeutic options. In this review, the interaction between nerves and cancer cells is described, including how cancer cells hijack and remodel nervous system structure and function, and how neuron-signaling regulates cancer cell growth directly or indirectly through modulating the TME. This evidence of the critical role of nerves in the malignant phenotype of tumors indicates the potential of using neuron-signaling targeting strategies in cancer treatment. By summarizing these findings, this review aims to provide comprehensive insights into the interaction between nerves and cancer cells, paving the way for neuron-signaling-based anticancer therapies.

Glioblastoma (GBM) is the most lethal brain tumor, characterized by strong resistance to conventional therapies. Despite recent therapeutic advancements, overcoming chemoresistance remains a major challenge. Here, we identified FOS-like antigen 1 (FOSL1) as a novel therapeutic target in GBM, particularly in patients with resistance to conventional drugs, including temozolomide (TMZ). FOSL1 gene was identified from the DepMap database as a potential mediator of TMZ resistance in GBM and found to be associated with chemoresistance molecular signatures and poor clinical outcomes. Functional analyses in GBM cells revealed that FOSL1 suppression enhanced apoptosis, induced G0/G1 cell cycle arrest, and reduced both cell migration and stemness marker expression. Transcriptomic profiling, including single-cell RNA-seq and bulk RNA-seq, highlighted the pivotal role of the interleukin-6 (IL-6)/STAT3 signaling pathway in FOSL1-mediated stemness. Mechanistically, in vitro experiments demonstrated that FOSL1 induces GBM stemness through IL-6-pSTAT3^Tyr705 signaling axis. Furthermore, vemurafenib, which targets FOSL1, was identified as a potential therapeutic agent against TMZ-resistant GBM in a mouse model. These findings suggest that FOSL1 promotes TMZ chemoresistance by regulating IL-6-pSTAT3^Tyr705-mediated stemness in GBM cells, making it a promising therapeutic target to overcome chemoresistance in GBM.

Graft-versus-host disease (GVHD) are still key obstacles of haploidentical transplantation. Interleukin-2 (IL-2) could promote natural killer (NK) cells and T-regulatory cells (Tregs) cells expansion in vitro and in vivo. We explored whether low-dose IL-2 administration at an early stage could promote NK cells and Tregs reconstitution and reduce GVHD after haplo-HSCT. This cohort trial included 10 recipients of accepting IL-2 treatment and case-pairing 30 recipients without IL-2 treatment post haplo-HSCT. In contrast to the control group, the 5-year incidence of chronic GVHD (cGVHD) was lower (p = 0.018), and GVHD progression-free survival (GPFS) was better (p = 0.025) in the IL-2 group. Blood NK-cells, Treg cells, conventional T cells (Tcon) cells, and the expression of CD62L+ on Tregs and Tcon cells reconstitution were increased post-IL-2 treatment. NKG2A expression on NK cells increased significantly post-IL-2 treatment. Meanwhile, IL-2 administration shortly increased the plasma levels of IFN-Ƴ, TNF-a, IL-10, and IL-2 in subjects post haplo-HSCT. Relative to the control group, low-dose IL-2 increased NK cell counts and the expression of CD122, DNAM-1, and NKG2D on NK cells post transplantation. Administration of low-dose IL-2 after haplo-HSCT correlated with reduced cGVHD, which should be explored further with randomized trial.

While thrombolytic therapy can be effective for stroke, many patients are unable to benefit due to time restrictions. In an aging society, sarcopenia, a condition marked by reduced muscle volume, often worsens recovery after stroke. Our study explored how mitochondria, which are abundant in muscle, could aid in stroke recovery through exercise-induced migration. Using mouse models of chronic hypoperfusion and ischemia, alongside in vitro studies with rat primary cells under oxygen–glucose deprivation and CoCl2 exposure, we found that treadmill exercise protected against white matter injury, myelin loss, astroglial formation, and memory deficits observed 28 days post-hypoperfusion. In acute ischemia models, training reduced glial activation and post-stroke complications. Exercise increased mitochondrial levels in muscle and blood, facilitating their migration between tissues via platelets. In vitro, the addition of muscle-derived mitochondria enhanced the survival of neurons, astrocytes, and oligodendrocytes. Notably, platelets carrying mitochondria from treadmill-trained mice significantly improved ischemic white matter injury and mitigated post-stroke complications. This study highlights mitochondria as a critical part of the secretome, suggesting that muscle-derived mitochondria might play a role in the protective effects of remote ischemic preconditioning. Cell–cell mitochondrial migration, therefore, could offer a promising new approach to reducing post-stroke complications and vascular dementia.

Conventional approaches for the detection and surveillance of non-muscle invasive bladder cancer (NMIBC) remain invasive, burdensome, and costly. The utLIFE-UC assay, designed to identify mutations and large copy number variations in urine, has demonstrated high accuracy in detecting urothelial carcinoma. Here, we assessed its efficacy in early detection of NMIBC, identifying minimal residual disease, and monitoring recurrence. Among 108 consecutive NMIBC patients evaluated, utLIFE-UC exhibited a sensitivity of 90.5% in diagnosing NMIBC, with comparable performance in detecting both de novo and recurrent NMIBC. For patients undergoing repeat transurethral resection of bladder tumor (Re-TURBT), the assay accurately identified all cases with residual tumor, achieving a 100% negative predictive value. Positive postoperative utLIFE-UC results before the first follow-up cystoscopy predicted a higher risk of future relapse. A positive test result at any time following TURBT was correlated with poorer recurrence-free survival, whereas sustained negative test results indicated recurrence-free status. Moreover, utLIFE-UC could predict recurrence with a median lead time of 73.5 days prior to clinical confirmation. As the first prospective, longitudinal analysis of urinary tumor DNA in NMIBC, this study highlights the potential of utLIFE-UC to enable earlier recurrence detection and improve risk stratification, potentially obviating unnecessary Re-TURBT and surveillance cystoscopies.

The Wnt signaling pathway deeply participates in multiple physiological and pathological processes. Its activity is intricately regulated by a diverse network of modulators, reflecting the pathway's structural and functional complexity. Dysregulation of Wnt signaling leads to cellular dysfunction and is associated with a wide spectrum of diseases, among which tissue fibrosis represents a major pathological outcome, characterized by activation of myofibroblasts and subsequent excessive deposition of extracellular matrix in response to injury. Wnt signaling is a central driver of fibrotic progression across multiple tissues and organs; however, effective therapeutic strategies directly targeting Wnt signaling in fibrosis remain scarce. In this review, we provide a comprehensive overview of Wnt pathway components, regulatory mechanisms, and therapeutic approaches. We systematically examine how Wnt signaling governs both developmental processes and pathological conditions, with particular emphasis on its role in fibrosis while also extending discussion to other diseases. Special attention is devoted to the secreted frizzled-related proteins (SFRPs) family, soluble regulators with biphasic, context-dependent effects that are especially relevant in fibrosis. Finally, we summarize insights from preclinical and clinical studies, review advances and challenges in the development of small-molecule compounds targeting Wnt components, highlighting the vital role of SFRPs as promising targets for antifibrotic intervention.

Systemic lupus erythematosus (SLE) is a chronic autoimmune disease affecting multiple organs and involving both innate and adaptive immunity. Dendritic cells (DCs) play a crucial role in linking innate and adaptive immune responses, and therefore they deeply participate in the initiation and development of SLE. Deleted in breast cancer-1 (DBC1) is a negative regulator of deacetylase SIRT1 (the mammalian homolog of silent information regulator 1) and involves in tissue inflammation. Roles of DBC1 in immune cells remain largely unknown, especially in DCs. We here identified that DBC1 is upregulated in activated DCs, and DBC1 deficiency weakened DC maturation while promoting B7-H1 expression. DC conditional knockout of DBC1 ameliorated murine lupus pathology by decreasing autoantibodies, complement C3, plasma cells, and follicular T helper (Tfh) cells, whereas promoting regulatory T-cell development. We further demonstrated that Dbc1^−/− DC lowered proinflammatory cytokine secretion such as IL-4, IL-6, and IL-12, and reduced signal transducer and activator of transcription 5 (STAT5) signal. With STAT5 overexpression, the protective effect by Dbc1^−/− DC was abolished in the lupus model. Therefore, targeting the DBC1-STAT5 axis in DCs diversifies the therapeutic strategies for SLE.