Spatiotemporal evolution of AML immune microenvironment remodeling and RNF149-driven drug resistance through single-cell multidimensional analysis.

BACKGROUND: The composition of the bone marrow immune microenvironment in patients with acute myeloid leukaemia (AML) was analysed by single-cell sequencing and the evolutionary role of different subpopulations of T cells in the development of AML and in driving drug resistance was explored in conjunction with E3 ubiquitin ligase-related genes. METHODS: To elucidate the mechanisms underlying AML-NR and Ara-C resistance, we analyzed the bone marrow immune microenvironment of AML patients by integrating multiple single-cell RNA sequencing datasets. When compared to the AML disease remission (AML-CR) cohort, AML-NR displayed distinct cellular interactions and alterations in the ratios of CD4+T, Treg, and CD8+T cell populations. RESULTS: Our findings indicate that the E3 ubiquitin ligase RNF149 accelerates AML progression, modifies the AML immune milieu, triggers CD8+T cell dysfunction, and influences the transformation of CD8+ Navie.T cells to CD8+TExh, culminating in diminished AML responsiveness to chemotherapeutic agents. Experiments both in vivo and in vitro revealed RNF149's role in enhancing AML drug-resistant cell line proliferation and in apoptotic inhibition, fostering resistance to Ara-C. CONCLUSION: In essence, the immune microenvironments of AML-CR and AML-NR diverge considerably, spotlighting RNF149's tumorigenic function in AML and cementing its status as a potential prognostic indicator and innovative therapeutic avenue for countering AML resistance.

Treatment-prognostication-adjustment a new therapeutic idea by analyzing T cell immune checkpoint in tumor microenvironment by algorithm: A bibliometric analysis.

To evaluate the temporal and spatial distribution of the knowledge network about tumor microenvironment and prognoses and explore new research hot spots and trends. Articles and reviews on tumor microenvironment and prognoses in the Web of Science journal from January 1999 to April 2022 were included. We used the CiteSpace and VOSviewer software to analyze the knowledge network composed of journals, institutions, countries, authors, and keywords. Frontiers in Immunology, Cancers, and Frontiers in Oncology have published more than 10% of articles in this field. China and the United States have contributed the most articles. Fudan University and Sun Yat-Sen University are the most active institutions. The authors in this field work closely; Zhang Wei and Douglas have made outstanding contributions. The three main research areas of tumor microenvironment and prognoses are microenvironment, prognosis, and immunotherapy. Until 2020, the main keywords were endothelial growth factor and adhesion. In the past three years, survival analysis, immune cell infiltration, and prediction model have been used. It can be seen that the focus in this field has shifted from tumor cell behavior and directly related molecules to prognosis prediction and non-tumor cells in the microenvironment. The future research trend may be to study the changes in the tumor microenvironment to predict the prognosis and guide the treatment. VOSviewer, CiteSpace, and Microsoft Excel 2019 were used to conduct a comprehensive visual analysis of the research on tumor environment and prognoses and provide valuable reference materials for researchers.

Global scientific trends on matrix metalloproteinase and osteosarcoma: A bibliometric and visualized analysis.

Objective: This study aimed to identify author, country, institutional, and journal collaborations and their impacts, assess the knowledge base, identify existing trends, and uncover emerging topics related to the role of Metalloproteinase in osteosarcoma. Methods: 945 Articles and reviews associated with the role of Metalloproteinase in osteosarcoma were obtained from the WoSCC and analyzed by Citespace and Vosviewer. Results: The main aspects of research on the role of MMP in OS are invasion and metastasis. The latest hotspots were found to be the mechanism of MMP promoting invasion and metastasis, lung metastasis, and antitumor activity. Notably, invasion, metastasis, and antitumor activity were potentially turning points in the MMP-OS field. In the future, the primary research hotspot in the field of MMP-OS may be to study the mechanism, explore their role in the OS lung metastasis, and determine their role in the cancer therapy process. Conclusion: This study thus offers a comprehensive overview of the MMP-OS-related field using bibliometrics and visual methods, which will provide a valuable reference for researchers interested in the field of MMP-OS.

5-ALA mediated photodynamic therapy with combined treatment improves anti-tumor efficacy of immunotherapy through boosting immunogenic cell death.

Photodynamic therapy (PDT) is clinically promising in destructing primary tumors and immunotherapy awakes host immunity to control distant metastases. 5-aminolevulinic acid (5-ALA), a smart photosensitizer, converts into a physiological PDT agent with no dark toxicity in vivo. In this study, we found for the first time 5-ALA-PDT induced colorectal cancer (CRC) cells death by immunogenic cell death (ICD) upon AKT inhibition. Dying cancer cells induced by 5-ALA-PDT efficiently activated bone-marrow derived dendritic cells (BMDCs). Simultaneously, autophagy was observed after AKT inhibition by 5-ALA-PDT. Besides, we found cells died more remarkable by ICD under a circumstance of low occurrence of autophagy. To evaluate the effects of 5-ALA-PDT in vivo, we applied subcutaneous tumor mouse model and delightedly found 5-ALA-PDT induced a systemic antitumor immune response to control both primary tumors and distant metastases. Meanwhile, 5-ALA-PDT enhanced Th1 immunity, leading cytotoxic T lymphocyte response, and raised tumor-specific T cells. Combining with Chloroquine (CQ), 5-ALA-PDT further augmented tumor-specific immunity effects indicating protective role of autophagy. Together, the combination therapy of 5-ALA-PDT and autophagy inhibitor synergistically led to a novel clinical approach and potential ICD-based tumor vaccine for CRC patients.

N6-Methyladenosine-Related LncRNAs Are Potential Remodeling Indicators in the Tumor Microenvironment and Prognostic Markers in Osteosarcoma.

N6-Adenosine methylation, yielding N6-methyladenosine (m6A), is a reversible epigenetic modification found in messenger RNAs and long non-coding RNAs (lncRNAs), which affects the fate of modified RNA molecules and is essential for the development and differentiation of immune cells in the tumor microenvironment (TME). Osteosarcoma (OS) is the most common primary bone tumor in children and adolescents, and is characterized by high mortality. Currently, the possible role of m6A modifications in the prognosis of OS is unclear. In the present study, we investigated the correlation between m6A-related lncRNA expression and the clinical outcomes of OS patients via a comprehensive analysis. Clinical and workflow-type data were obtained from the Genotype-Tissue Expression Program and The Cancer Genome Atlas. We examined the relationship between m6A modifications and lncRNA expression, conducted Kyoto Encyclopedia of Genes analysis and also gene set enrichment analysis (GSEA), implemented survival analysis to investigate the association of clinical survival data with the expression of m6A-related lncRNAs, and utilized Lasso regression to model the prognosis of OS. Furthermore, we performed immune correlation analysis and TME differential analysis to investigate the infiltration levels of immune cells and their relationship with clinical prognosis. LncRNA expression and m6A levels were closely associated in co-expression analysis. The expression of m6A-related lncRNAs was quite low in tumor tissues; this appeared to be a predicting factor of OS in a prognostic model, independent of other clinical features. The NOD-like receptor signaling pathway was the most significantly enriched pathway in GSEA. In tumor tissues, SPAG4 was overexpressed while ZBTB32 and DEPTOR were downregulated. Tissues in cluster 2 were highly infiltrated by plasma cells. Cluster 2 presented higher ESTIMATE scores and stromal scores, showing a lower tumor cell purity in the TME. In conclusion, m6A-related lncRNA expression is strongly associated with the occurrence and development of OS, and can be used to as a prognostic factor of OS. Moreover, m6A-related lncRNAs and infiltrating immune cells in the TME could serve as new therapeutic targets and prognostic biomarkers for OS.