Diverse intratumoral heterogeneity and immune microenvironment of two HPV‐related cervical cancer types revealed by single‐cell RNA sequencing

Abstract

Cervical squamous cell carcinoma (SCC) and adenocarcinoma (AD) are the main histological types of human papillomavirus-related cervical cancer. However, there are few reports on cell type-specific molecular differences between SCC and AD.Here, we used unbiased droplet-based single-cell RNA sequencing to elucidate the cellular differences between SCC and AD in tumor heterogeneity, and tumor microenvironment (TME). A total of 61 723 cells from three SCC and three AD patients, were collected and divided into nine cell types. Epithelial cells exhibited high intra-and interpatient heterogeneity and functional diversity. Signaling pathways, such as epithelial-to-mesenchymal-transition (EMT), hypoxia and inflammatory response were upregulated in SCC, while cell cycle-related signaling pathways were highly enriched in AD. SCC was associated with high infiltration of cytotoxicity CD8 T, effector memory CD8 T, proliferative natural killer (NK), and CD160+ NK cells as well as tumor-associated macrophages (TAMs) with high major histocompatibility complex-II genes. AD exhibited a high proportion of naive CD8 T, naive CD4 T, Treg CD4, central memory CD8, and TAMs with immunomodulatory functions. Additionally, we also observed that the majority of cancer-associated fibroblasts (CAFs) were from AD, and participated in inflammation regulation, while SCC-derived CAFs exhibited similar functions to tumor cells, such as EMT and hypoxia. This study revealed the widespread reprogramming of multiple cell populations in SCC and AD, dissected the cellular heterogeneity and characteristics in TME, and proposed potential therapeutic strategies for CC, such as targeted therapy and immunotherapy.

STING agonist inflames the cervical cancer immune microenvironment and overcomes anti-PD-1 therapy resistance

“…Additionally, they present a diminished expression profile in cervical adenocarcinoma compared to squamous cervical carcinoma both in TCGA dataset ( Figures 1M–O ) and the GSE192897 dataset ( Figures 1P–R ). Previous studies demonstrated that cervical adenocarcinoma possessed a heightened malignant propensity, and a greater inclination toward metastatic behavior ( 45 ), characterized by the TME with a more robust immune infiltration cells profile ( 46 ). These findings underscore the pivotal role of the STING pathway in shaping the prognosis of cervical cancer.…”

Domain generalization enables general cancer cell annotation in single-cell and spatial transcriptomics

“…3e (full names of the cancers are detailed in Supplementary Table 15 ), where it can be seen that the marker candidates identified using this strategy are consistent with available knowledge. For instance, EPCAM, KRT8, KRT18 are widely employed markers for malignant cell or cancer stem cell across various malignancies such as cervical cancer 37 , breast cancer 38 and head & neck cancer 39 , and SOX2 was considered as a cancer markers in glioblastomas 40 and esophageal squamous cell carcinoma 41 .…”

Advances in HPV‐associated tumor management: Therapeutic strategies and emerging insights

“…Moreover, the advancements and application of single-cell sequencing and deep learning networks have provided additional potential biomarkers for the diagnosis and prognosis of HPV-related tumors. 17 Traditional treatment modalities for CC include surgery, chemotherapy, radiotherapy, and targeted immunotherapy. In recent years, new therapies such as immune checkpoint inhibitors (ICIs), antiangiogenic agents, and therapeutic vaccines have emerged, resulting in a significant improvement in survival rates and prognosis for CC patients.…”