Abstract
Cervical squamous cell carcinoma is one of the most common causes of female cancer deaths worldwide. At present, immunotherapy using immune checkpoint blockade (ICB) has improved the prognosis of many cancer patients, and neoantigens generated by mutations may serve as potential biomarkers for predicting the outcome of ICB therapy. In this study, we identified missense mutations as the most frequent in landscapes of gene mutation in cervical squamous cell carcinoma (CESC) samples. Patients with higher tumor mutation burden (TMB) presented higher overall survival (OS). In addition, there was a significant correlation between the high TMB group and fractions of most immune cells. Univariate and multivariate Cox regression analyses identified five hub genes (IFNG, SERPINA3, CCL4L2, TNFSF15, and IL1R1) that were used to build a prognostic model. In the prognostic model, the low-risk group achieved better OS. Mutations in the five hub genes mainly affected the infiltration level of CD8+ T cells and dendritic cells. In conclusion, our study is valuable for exploring the role of TMB and its relationship with immune infiltration in CESC. Moreover, the prognosis model may help predict the sensitivity of patients to immunotherapy and provide underlying biomarkers for personalized immunotherapy.
Highlights
Cervical squamous cell carcinoma (CESC) is a female cancer with high morbidity and mortality
Riaz et al demonstrated that insufficient expression of mismatch repair (MMR) mechanisms increased the number of tumor cells presenting encoded and mutation-associated neoantigens, which can be recognized by the immune system of the body [5]
The results revealed that the scores associated with the T-cell inflammation signature (TIS) and tumor immune dysfunction and exclusion (TIDE) profiles of immune checkpoints in the low-risk group were higher than those in the high-risk group, such as APC co-inhibition, cytokine–cytokine receptor (CCR), CD8+ T cells, Check-point, Cytolytic activity, HLA, Inflammation-promoting, MHC class I, Parainflammation, T cell co-inhibition, T cell co-stimulation, T helper cells, Tfh, Th1 cells, Th2 cells, tumor-infiltrating leukocytes (TILs), Treg, Type I IFN response, and Type II IFN response (Figure 10A)
Summary
Cervical squamous cell carcinoma (CESC) is a female cancer with high morbidity and mortality. Studies have shown that cervical squamous cell carcinoma (CESC) can occur in women of different ages, the average age at diagnosis is lower than that of most cancers [1]. Immune checkpoint blockade immunotherapy can effectively induce anti-tumor immunity of different solid tumors, few patients benefit from the treatment. Tumor cells damage the immune system of the body through a variety of suppression mechanisms, such as activation of immune regulatory checkpoints [3]. Immune checkpoint blockade (ICB) treatment can reactivate the cytolytic potential of cytotoxic T cells and increase the effective elimination of tumor cells by interrupting dysfunctional “self-tolerance” signaling. Identifying a population of patients who are more likely to benefit from new antibodies produced by nonsynonymous mutations is becoming increasingly important in clinical research
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