Integrated immunological analysis of single-cell and bulky tissue transcriptomes reveals the role of interactions between M0 macrophages and naïve CD4+ T cells in the immunosuppressive microenvironment of cervical cancer

Abstract

In recent decades, the incidence and mortality of cervical cancer have declined in developed countries due to the implementation of screening and vaccination programs. However, cervical cancer remains one of the major culprits of cancer-related deaths in young women. Current studies have found that immune cell-related intercellular communication in the tumor microenvironment has a large impact on the construction of the immunosuppressive microenvironment. In this study, we performed a comprehensive immune analysis on bulk RNA-seq and scRNA-seq data obtained from cervical cancer and revealed that two highly plastic cell populations, M0 macrophages and naïve CD4⁺ T cells, were significantly correlated with prognosis and clinical phenotypes. Notably, signaling between M0 macrophages and naïve CD4⁺ T cells as well as intracellular transcription factor activity were significantly altered in the tumor state. Furthermore, we identified overlapping genes between the transcription factor target genes of M0 macrophages or naïve CD4⁺ T cells and the differentially expressed genes in each type of cell, and these overlapping genes were subsequently subjected to an analysis using the LASSO regression model. Finally, we generated a score index that was significantly associated with the clinical prognosis of cervical cancer. In conclusion, interventions to improve the communication between M0 macrophages and naïve CD4⁺ T cells may help to improve the immunosuppressive microenvironment of cervical cancer and prevent immune evasion. The relevant molecular mechanisms need to be further validated by experimental and cohort studies.

Keywords: Cervical cancer; Immunosuppressive microenvironment; Intercellular communication; M0 macrophages; Naïve CD4(+) T cells.