RESUMO
Background: The prognostic value of programmed cell death ligand 1 (PD-L1) expression and tumor-infiltrating lymphocytes (TILs) in high-grade serous ovarian cancer (HGSOC) remains a controversial topic in the research field. To comprehensively assess the importance of PD-L1 and TILs in this particular subtype of ovarian cancer, we performed a meta-analysis. Methods: We conducted a comprehensive search of PubMed, Embase, Scopus, Web of Science, and Cochrane Library databases up to December 25, 2022. The association between PD-L1, TILs, and survival outcomes was evaluated using the combined hazard ratios (HRs) and their corresponding 95% confidence intervals (CIs). Results: This meta-analysis comprised 11 trials involving a total of 1746 cases. The results revealed no significant association between PD-L1 expression in tumor cells (TCs) and overall survival (OS, HR = 0.76, 95% CI: 0.52-1.09, p = 0.136) or progression-free survival (PFS, HR = 0.71, 95% CI: 0.4 -1.24, p = 0.230). Nevertheless, a correlation was observed between PD-L1 expression in immune cells (ICs) and OS (HR = 0.73, 95% CI: 0.55-0.97, p = 0.031). Furthermore, the presence of CD8+ and PD-1+ TILs was found to significantly enhance OS (HR = 0.70, 95% CI = 0.55-0.87, p = 0.002; HR = 0.57, 95% CI = 0.40-0.80, p = 0.001, respectively) and PFS (HR = 0.62, 95% CI = 0.41-0.92, p = 0.019; HR = 0.52, 95% CI = 0.35-0.78, p = 0.002, respectively), whereas the presence of CD3+ and CD4+ TILs was positively associated with OS (HR = 0.50, 95% CI = 0.29-0.87, p = 0.014; HR = 0.55, 95% CI = 0.34-0.91, p = 0.020, respectively). Conclusion: This study indicates a positive correlation between ICs-derived PD-L1 and survival, while no significant correlation was observed between TCs-derived PD-L1 and prognosis. These results highlight the importance of studying PD-L1 expression in ICs as a prognostic predictor. In addition, the presence of TILs was found to significantly improve patient survival, suggesting that TILs may be a valuable prognostic biomarker. Systematic review registration: https://www.crd.york.ac.uk/prospero/, identifier CRD42022366411.
RESUMO
Bacterial translocation is a pathological process involving migration of pathogenic bacteria across the intestinal barrier to enter the systemic circulation and gain access to distant organs. This phenomenon has been linked to a diverse range of diseases including inflammatory bowel disease, pancreatitis, and cancer. The intestinal barrier is an innate structure that maintains intestinal homeostasis. Pathogenic infections and dysbiosis can disrupt the integrity of the intestinal barrier, increasing its permeability, and thereby facilitating pathogen translocation. As translocation represents an essential step in pathogenesis, a clear understanding of how barrier integrity is disrupted and how this disruption facilitates bacterial translocation could identify new routes to effective prophylaxis and therapy. In this comprehensive review, we provide an in-depth analysis of bacterial translocation and intestinal barrier function. We discuss currently understood mechanisms of bacterial-enterocyte interactions, with a focus on tight junctions and endocytosis. We also discuss the emerging concept of bidirectional communication between the intestinal microbiota and other body systems. The intestinal tract has established 'axes' with various organs. Among our regulatory systems, the nervous, immune, and endocrine systems have been shown to play pivotal roles in barrier regulation. A mechanistic understanding of intestinal barrier regulation is crucial for the development of personalized management strategies for patients with bacterial translocation-related disorders. Advancing our knowledge of barrier regulation will pave the way for future research in this field and novel clinical intervention strategies.
