Comprehensive analysis of the immunogenomic landscape and clinical features in cervical cancer

Abstract

AbstractImmunotherapy has changed the standard of treatment for many cancers. However, the same treatments showed disappointing outcomes in cervical cancer so far. Thus, understanding the mechanisms that support the immune tolerance of cervical cancer will provide a way to design new strategies to enhance immunotherapies. Here, we characterized cellular compositions of the immune infiltrates in cervical cancer and investigated if the tumor immune landscape is a predictor for patient prognosis. The fraction of ten immune infiltrates of cervical and other cancers were analyzed by using QuanTIseq software base on the bulk mRNA sequencing data from The Cancer Genome Atlas Program (TCGA). Cervical cancer is one of the cancers that had the lowest percentage of total immune infiltrates, but it had the highest ratio for CD8 T cells to all immune infiltrates among all solid cancers. Both the principal components (PCA) analysis and heatmap with dendrogram analysis showed that cervical cancer had a similar immune infiltrated microenvironment with other squamous cell carcinomas, such as head and neck cancer and lung squamous cell cancer. The PCA and heatmap with dendrogram analysis showed that cervical cancer and HPV positive head and neck cancers were clustered more closer and partially separated with HPV negative head and neck cancer. Further analysis showed that HPV-positive cervical and head and neck cancers had a significantly higher level of CD8 T cells and M1-liked macrophages, but a lower level of M2 macrophages. The survival analysis showed that a higher level of CD8 T cells was associated with a better patient prognosis. However, immuno-suppressive immune infiltrates including M2 macrophages and Treg cells that are known to suppress anti-tumor immunity also demonstrated positive patient overall survival. Our study provided a conceptual framework to understand the tumor immune microenvironment of cervical cancer. Our results also demonstrated that the immune infiltrates can be a prognosis marker for cervical cancer.Simple SummaryCervical cancer is the most common gynecologic cancer and the fourth leading cause of cancer-related death in women worldwide. There are relatively limited treatment options for late-stage cervical cancer. Immunotherapy is a new therapeutic treatment developed with great success in treating many cancers, but the same treatment has not been producing satisfactory results in many cases of cervical cancer. In the present study, we provided a comprehensive immune characterization specifically for cervical cancer. We determined the prognostic value of a specific subtype of tumor-infiltrating immune cells for clinical outcomes and demonstrated that HPV infection affected the immune cell infiltration and induce pro-inflammatory phenotypes. Our study provides a systematic insight into the tumor immune microenvironment of cervical cancers and offers a conceptual framework for the future design of rational combination treatment strategies to improve immunotherapy outcomes.