Cervical cancer immune infiltration microenvironment identification, construction of immune scores, assisting patient prognosis and immunotherapy

Abstract

BackgroundThe immune microenvironment is of great significance in cervical cancer. However, there is still a lack of systematic research on the immune infiltration environment of cervical cancer.MethodsWe obtained cervical cancer transcriptome data and clinical information from the Cancer Genome Atlas (TCGA) and the Gene Expression Omnibus (GEO) databases, evaluated the immune microenvironment of cervical cancer, determined immune subsets, constructed an immune cell infiltration scoring system, screened key immune-related genes, and performed single-cell data analysis and cell function analysis of key genes.ResultsWe combined the TCGA and GEO data sets and obtained three different immune cell populations. We obtained two gene clusters, extracted 119 differential genes, and established an immune cell infiltration (ICI) scoring system. Finally, three key genes, IL1B, CST7, and ITGA5, were identified, and single-cell sequencing data were mined to distribute these key genes in different cell types. By up-regulating CST7 and down-regulating IL1B and ITGA5, cervical cancer cells’ proliferation ability and invasion ability were successfully reduced.ConclusionWe conducted a comprehensive assessment of the state of the tumor immune microenvironment in cervical cancer, constructed the ICI scoring system, and identified the ICI scoring system as a potential indicator of susceptibility to immunotherapy for cervical cancer, identifying key genes suggesting that IL1B, CST7, and ITGA5 play an essential role in cervical cancer.

KIF23 promotes cervical cancer progression via inhibiting NLRP3‐mediated pyroptosis

“…26 Therefore, the tumor immune microenvironment plays a pivotal significance in CC. 27 In our study, KIF23 and CEP55 were found to be positively correlated with tumor purity. Similarly, EZH2 had a positive correlation with CD4 + T cells and MELK with neutrophils and dendritic cells.…”

“…In a variety of malignancies, the histone methyl transferase EZH2 has pro‐oncogenic and immunomodulatory effects 26 . Therefore, the tumor immune microenvironment plays a pivotal significance in CC 27 . In our study, KIF23 and CEP55 were found to be positively correlated with tumor purity.…”

TIME Is Ticking for Cervical Cancer

“…PD-1/PD-L1 overexpression (T cells, DCs, and macrophages) is well correlated with high-risk HPV infection and its progression to the CC with increased mortality by supporting the immunosuppressive TIME (Figure 3) [110,[112][113][114][115][116][117]. Cytotoxic T-lymphocyteassociated protein 4 (CTLA-4, another immune checkpoint) overexpression is also associated with CC immunosuppressive TIME (Figure 3) by increasing regulatory T cells' (T regs ) and conventional T cells' antitumor function by regulating CD28 signaling that impacts their interaction with CD80 (B7.1) and CD86 (B7.2) [118,119]. Increased CTLA4 levels also correlate with IL-1β expression CC as IL-1β increases the signal transduction of the CTLA4; therefore, targeting the IL-1β-CTLA4 axis may help to overcome the CC immunosuppressive TIME, as seen in colon cancer [118,120].…”

“…Cytotoxic T-lymphocyteassociated protein 4 (CTLA-4, another immune checkpoint) overexpression is also associated with CC immunosuppressive TIME (Figure 3) by increasing regulatory T cells' (T regs ) and conventional T cells' antitumor function by regulating CD28 signaling that impacts their interaction with CD80 (B7.1) and CD86 (B7.2) [118,119]. Increased CTLA4 levels also correlate with IL-1β expression CC as IL-1β increases the signal transduction of the CTLA4; therefore, targeting the IL-1β-CTLA4 axis may help to overcome the CC immunosuppressive TIME, as seen in colon cancer [118,120]. Cystatin 7 (CST7) in T cells is also downregulated in the CC patients which induces dysfunctional antitumor CD4 + and CD8 + T cell immunity [118,121].…”

“…Increased CTLA4 levels also correlate with IL-1β expression CC as IL-1β increases the signal transduction of the CTLA4; therefore, targeting the IL-1β-CTLA4 axis may help to overcome the CC immunosuppressive TIME, as seen in colon cancer [118,120]. Cystatin 7 (CST7) in T cells is also downregulated in the CC patients which induces dysfunctional antitumor CD4 + and CD8 + T cell immunity [118,121]. These dysfunctional CD8 + T cells comprise the major T-cell population in the CC TIME.…”