Cervical squamous cell carcinoma (CESC) is a prototypical human cancer with well-characterized pathological stages of initiation and progression. However, high-resolution knowledge of the transcriptional programs underlying each stage of CESC is lacking, and important questions remain. We performed single-cell RNA sequencing of 76,911 individual cells from 13 samples of human cervical tissues at various stages of malignancy, illuminating the transcriptional tumorigenic trajectory of cervical epithelial cells and revealing key factors involved in CESC initiation and progression. In addition, we found significant correlations between the abundance of specific myeloid, lymphoid, and endothelial cell populations and the progression of CESC, which were also associated with patients’ prognosis. Last, we demonstrated the tumor-promoting function of matrix cancer–associated fibroblasts via the NRG1-ERBB3 pathway in CESC. This study provides a valuable resource and deeper insights into CESC initiation and progression, which is helpful in refining CESC diagnosis and for the design of optimal treatment strategies.
2 February 2024 in Journal of Experimental & Clinical Cancer Research
Tumor-infiltrating T cells recognize, attack, and clear tumor cells, playing a central role in antitumor immune response. However, certain immune cells can impair this response and help tumor immune escape. Therefore, exploring the factors that influence T-cell infiltration is crucial to understand tumor immunity and improve therapeutic effect of cancer immunotherapy. The use of single-cell RNA sequencing (scRNA-seq) allows the high-resolution analysis of the precise composition of immune cells with different phenotypes and other microenvironmental factors, including non-immune stromal cells and the related molecules in the tumor microenvironment of various cancer types. In this review, we summarized the research progress on T-cell infiltration and the crosstalk of other stromal cells and cytokines during T-cell infiltration using scRNA-seq to provide insights into the mechanisms regulating T-cell infiltration and contribute new perspectives on tumor immunotherapy.
Purpose: We aimed to investigate the relationship between pretreatment neutrophil-to-lymphocyte ratio (NLR)/platelet-to-lymphocyte ratio (PLR) and the estimation of hormone-receptor-negative (HR-) breast cancer patients’ survival in a Chinese cohort. Patients and methods: Of 434 consecutive HR- nonmetastatic breast cancer patients treated between 2004 and 2010 in the Affiliated Hospital of Academy of Military Medical Sciences, 318 eligible cases with complete data were included in the present study. Kaplan–Meier analysis was performed to determine the overall survival (OS) and disease-free survival (DFS). Univariate and multivariate Cox proportional hazards models were used to test the usefulness of NLR and PLR. Results: Univariate analysis indicated that both elevated NLR and PLR (both P<0.001) were associated with poor OS. The utility of NLR remained in the multivariate analysis (P<0.001), but not PLR (P=0.104). The analysis results for DFS were almost the same as OS. Subgroup analysis revealed a significant association between increased NLR and PLR (P<0.001 and P=0.011) and poor survival in triple-negative breast cancer. However, for human epidermal growth factor receptor 2-positive breast cancer, only NLR was significantly associated with OS in the multivariate analysis (P=0.001). Conclusion: The present study indicates that both increased NLR and PLR are associated with poor survival in HR- breast cancer patients. Meanwhile, NLR is independently correlated with OS and DFS, but PLR is not.
Aim: We aimed to evaluate the prognostic values of neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), lymphocyte-to-monocyte ratio (LMR) and systemic immune-inflammation inde...
14 February 2025 in Journal of Translational Medicine
Recent oncological research has intensely focused on the tumor immune microenvironment (TME), particularly the functions of CD4 + T lymphocytes. CD4+ T lymphocytes have been implicated in antigen presentation, cytokine release, and cytotoxicity, suggesting their contribution to the dynamics of the TME. Furthermore, the application of single-cell sequencing has yielded profound insights into the phenotypic diversity and functional specificity of CD4+ T cells in the TME. In this review, we discuss the current findings from single-cell analyses, emphasizing the heterogeneity of CD4+ T cell subsets and their implications in tumor immunology. In addition, we review the critical signaling pathways and molecular networks underpinning CD4+ T cell activities, thereby offering novel perspectives on therapeutic targets and strategies for cancer treatment and prognosis.
The relationship between the immune cell and tumor occurrence and progression remains unclear. Profiling alterations in the tumor immune microenvironment (TIME) at high resolution is crucial to identify factors influencing cancer progression and enhance the effectiveness of immunotherapy. However, traditional sequencing methods, including bulk RNA sequencing, exhibit varying degrees of masking the cellular heterogeneity and immunophenotypic changes observed in early and late-stage tumors. Single-cell RNA sequencing (scRNA-seq) has provided significant and precise TIME landscapes. Consequently, this review has highlighted TIME cellular and molecular changes in tumorigenesis and progression elucidated through recent scRNA-seq studies. Specifically, we have summarized the cellular heterogeneity of TIME at different stages, including early, late, and metastatic stages. Moreover, we have outlined the related variations that may promote tumor occurrence and metastasis in the single-cell era. The widespread applications of scRNA-seq in TIME will comprehensively redefine the understanding of tumor biology and furnish more effective immunotherapy strategies.