Infiltration Patterns of Cervical Epithelial Microenvironment Cells During Carcinogenesis

Abstract

BackgroundLocal cellular microenvironment plays a crucial role in the HPV-induced cervical malignant transformation. Characterization of the dynamic infiltration changes of microenvironment cells during cervical carcinogenesis would contribute to a better understanding of involved mechanisms.MethodsThree public gene expression datasets of cervical squamous epithelium samples were collected and combined. We applied seven up-to-date computational methods for infiltrating estimation and compared their results (CD4+ and CD8+ T cells) to the known fraction. After benchmarking the applied methods, the cell filtration patterns were determined and clustered through fuzzy c-means algorithm.ResultsMost methods displayed better performance in predicting the abundance of CD4+ T cell than that of CD8+ T cell. The infiltration patterns of 33 microenvironment cell types (including 31 immune cells and 2 non-immune cells) were determined, and five immune cell clusters with distinct features were then derived. Meanwhile, opposite changes in abundance were observed between the activated and resting state of some immune cells from the progression perspective.ConclusionsBased on characteristics and evaluation performance of different methods, as well as previous findings, for the first time we provide a comprehensive overview of the infiltration patterns of microenvironment cells throughout cervical cancer progression.

TIME Is Ticking for Cervical Cancer

“…For example, Th1 levels increase from low to high-grade squamous intraepithelial lesions but deplete from high-grade squamous intraepithelial lesions to SCC. In contrast, Th2 levels deplete from low-to high-grade squamous intraepithelial lesions [221]. Th2 and Th17 populations increase, and Th1 levels are depleted in CIN and CC, which supports that a shift in these cell populations starts prior to CC formation and, thus, contributes to CIN progressing into CC (Figure 1B) [222].…”

“…cDC1s are critical for antitumor cytotoxic T cells and decrease T regs via secreting the cGAS/STING signaling pathway-dependent type 1 IFNs [221]. The cDC1s' decrease in the CAC TIME is associated with poor patient survival due to impaired T-cell-mediated antitumor immunity (Figures 1B and 3) [222].…”

Exploring the role of disulfidptosis-related signatures in immune microenvironment, prognosis and therapeutic strategies of cervical cancer

“…Comprehensive clinical data, including survival information and gene-level frequency of copy number variations (CNVs), were sourced from a prior study [13] . For external validation, the series matrix file of GSE52903 ( n = 72) was downloaded from the Gene Expression Omnibus (GEO), and the processed expression matrix of GSE63514 ( n = 128) was acquired from a previous study [14] .…”

“…Immune, stromal and ESTIMATE scores were calculated via the ESTIMATE algorithm [19] . CIBERSORTX-Absolute scores were obtained and processed as previously described [14] .…”

Sequencing-based transcriptome analysis reveals diversification of immune response- and angiogenesis-related expression patterns of early-stage cervical carcinoma as compared with high-grade CIN

“…At the same time, with the establishment of cervical microcarcinoma and its progression to invasive cancer, a marked increase in the diversity of co-expression meta-programs and immune heterogeneity, as well as global upregulation of interferon responses has been recently reported ( 25 ). Another source of complexity of CeCa immune landscape can be the recently described non-linear alterations of its specific components (such as regulatory and memory T cells) during progression from intraepithelial lesions to invasive cancer ( 26 ). However, since most CeCa molecular profiling studies addressed more advanced, metastatic, and recurrent disease stages, these data need to be additionally supported by enrollment of earlier clinical and preclinical stages.…”