A comparative study of the cellular immune response in patients with stage IB cervical squamous cell carcinoma. Low numbers of several immune cell subtypes are strongly associated with relapse of disease within 5 years

2008 ◽  
Vol 108 (1) ◽  
pp. 106-111 ◽  
Author(s):  
Bettina S. Nedergaard ◽  
Morten Ladekarl ◽  
Jens Randel Nyengaard ◽  
Karsten Nielsen
2021 ◽  
Vol 19 (1) ◽  
Author(s):  
Yimin Li ◽  
Shun Lu ◽  
Shubin Wang ◽  
Xinhao Peng ◽  
Jinyi Lang

Abstract Background The main limitation of current immune checkpoint inhibitors (ICIs) in the treatment of cervical cancer comes from the fact that it benefits only a minority of patients. The study aims to develop a classification system to identify immune subtypes of cervical squamous cell carcinoma (SCC), thereby helping to screen candidates who may respond to ICIs. Methods A real-world cervical SCC cohort of 36 samples were analyzed. We used a nonnegative matrix factorization (NMF) algorithm to separate different expression patterns of immune-related genes (IRGs). The immune characteristics, potential immune biomarkers, and somatic mutations were compared. Two independent data sets containing 555 samples were used for validation. Results Two subtypes with different immunophenotypes were identified. Patients in sub1 showed favorable progression-free survival (PFS) and overall survival (OS) in the training and validation cohorts. The sub1 was remarkably related to increased immune cell abundance, more enriched immune activation pathways, and higher somatic mutation burden. Also, the sub1 group was more sensitive to ICIs, while patients in the sub2 group were more likely to fail to respond to ICIs but exhibited GPCR pathway activity. Finally, an 83-gene classifier was constructed for cervical SCC classification. Conclusion This study establishes a new classification to further understand the immunological diversity of cervical SCC, to assist in the selection of candidates for immunotherapy.


2021 ◽  
Author(s):  
Zhihua Ou ◽  
Shitong Lin ◽  
Jiaying Qiu ◽  
Wencheng Ding ◽  
Peidi Ren ◽  
...  

To understand the etiological, structural, and immunological characteristics of cervical squamous cell carcinoma (CSCC), we conducted single nucleus RNA sequencing (snRNA-seq) and spatial transcriptomics (ST) experiments for cervical samples from 20 individuals. When exploring the possible factors shaping the intra-individual immune heterogeneity in CSCC, we identified a cluster of cancer-associated fibroblasts (CAFs) enriched around some tumors, which highly expressed ACTA2, POSTN, ITGB4, and FAP. Results showed that the CAFs might support the growth and metastasis of tumors by inhibiting lymphocyte infiltration and remodeling the tumor extracellular matrix. Moreover, high CAF signals predicted poorer clinical outcomes for CSCC patients. Our data also revealed the infection profiles of HPV in tumors, the critical factors involved in the progression of cervical cancerous lesions, and the association between tumor metabolism and immune response intensity. Collectively, our findings may improve the prognostic and therapeutic methods for CSCC.


2018 ◽  
Vol 19 (11) ◽  
pp. 3607 ◽  
Author(s):  
Xia Li ◽  
Yunpeng Cai

Cervical cancer is traditionally classified into two major histological subtypes, cervical squamous cell carcinoma (CSCC) and cervical adenocarcinoma (CA). However, heterogeneity exists among patients, comprising possible subpopulations with distinct molecular profiles. We applied consensus clustering to 307 methylation samples with cervical cancer from The Cancer Genome Atlas (TCGA). Fisher’s exact test was used to perform transcription factors (TFs) and genomic region enrichment. Gene expression profiles were downloaded from TCGA to assess expression differences. Immune cell fraction was calculated to quantify the immune cells infiltration. Putative neo-epitopes were predicted from somatic mutations. Three subclasses were identified: Class 1 correlating with the CA subtype and Classes 2 and 3 dividing the CSCC subtype into two subclasses. We found the hypomethylated probes in Class 3 exhibited strong enrichment in promoter region as compared with Class 2. Five TFs significantly enriched in the hypomethylated promoters and their highly expressed target genes in Class 3 functionally involved in the immune pathway. Gene function analysis revealed that immune-related genes were significantly increased in Class 3, and a higher level of immune cell infiltration was estimated. High expression of 24 immune genes exhibited a better overall survival and correlated with neo-epitope burden. Additionally, we found only two immune-related driver genes, CARD11 and JAK3, to be significantly increased in Class 3. Our analyses provide a classification of the largest CSCC subtype into two new subclasses, revealing they harbored differences in immune-related gene expression.


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