Investigator

Liang Weng

Peking University

LWLiang Weng
Papers(2)
Single-cell profiling…Exploring Cervical Ad…
Collaborators(1)
Congrong Liu
Institutions(1)
Peking University

Papers

Single-cell profiling reveals the intratumor heterogeneity and immunosuppressive microenvironment in cervical adenocarcinoma

Background:Cervical adenocarcinoma (ADC) is more aggressive compared to other types of cervical cancer (CC), such as squamous cell carcinoma (SCC). The tumor immune microenvironment (TIME) and tumor heterogeneity are recognized as pivotal factors in cancer progression and therapy. However, the disparities in TIME and heterogeneity between ADC and SCC are poorly understood.Methods:We performed single-cell RNA sequencing on 11 samples of ADC tumor tissues, with other 4 SCC samples served as controls. The immunochemistry and multiplexed immunofluorescence were conducted to validate our findings.Results:Compared to SCC, ADC exhibited unique enrichments in several sub-clusters of epithelial cells with elevated stemness and hyper-malignant features, including the Epi_10_CYSTM1 cluster. ADC displayed a highly immunosuppressive environment characterized by the enrichment of regulatory T cells (Tregs) and tumor-promoting neutrophils. The Epi_10_CYSTM1 cluster recruits Tregs via ALCAM-CD6 signaling, while Tregs reciprocally induce stemness in the Epi_10_CYSTM1 cluster through TGFβ signaling. Importantly, our study revealed that the Epi_10_CYSTM1 cluster could serve as a valuable predictor of lymph node metastasis for CC patients.Conclusions:This study highlights the significance of ADC-specific cell clusters in establishing a highly immunosuppressive microenvironment, ultimately contributing to the heightened aggressiveness and poorer prognosis of ADC compared to SCC.Funding:Funded by the National Natural Science Foundation of China (82002753; 82072882; 81500475) and the Natural Science Foundation of Hunan Province (2021JJ40324; 2022JJ70103).

Exploring Cervical Adenocarcinoma: Epidemiological Insights, Diagnostic and Therapeutic Challenges, and Pathogenetic Mechanisms

ABSTRACTBackgroundCervical cancer poses a significant threat to women's health and encompasses various histological types, including squamous cell carcinoma (SCC), cervical adenocarcinoma (CA), and adenosquamous carcinoma. CA, in particular, presents a formidable challenge in clinical management due to its low early detection rate, pronounced aggressiveness, high recurrence rate, and mortality, compounded by the complexities associated with late‐stage treatment. There is limited understanding of the similarities and differences in the pathogenesis mechanisms between CA and SCC, such as tumor heterogeneity and the tumor immune microenvironment (TME).MethodsA literature search was carried out in the PubMed, Web of Science, and Google Scholar databases using the following research terms: “gynecological oncology,” “cervical cancer,” “cervical adenocarcinoma,” “epidemiology,” “diagnosis and treatment of cervical adenocarcinoma,” “Human papillomavirus,” “World Health Organization,” “tumor microenvironment,” “single‐cell RNA sequencing,” “molecular mechanism,” and “preclinical research model.”ConclusionThis review consolidates the epidemiological characteristics, diagnostic and therapeutic hurdles, and the latest advances in research on CA. It aims to highlight the significant heterogeneity of the TME characteristics exhibited by CA compared to SCC. Additionally, we also summarize the common preclinical models for CA and discuss the advantages and disadvantages of using various models in research. We aspire that the discussions presented herein will offer novel insights and directions for subsequent research, as well as clinical diagnosis and treatment strategies for CA.

2Papers
1Collaborators