Single-cell RNA-sequencing reveals radiochemotherapy-induced innate immune activation and MHC-II upregulation in cervical cancer

Abstract

Radiochemotherapy (RCT) is a powerful treatment for cervical cancer, which affects not only malignant cells but also the immune and stromal compartments of the tumor. Understanding the remodeling of the local ecosystem induced by RCT would provide valuable insights into improving treatment strategies for cervical cancer. In this study, we applied single-cell RNA-sequencing to paired pre- and post-RCT tumor biopsies from patients with cervical cancer and adjacent normal cervical tissues. We found that the residual population of epithelial cells post-RCT showed upregulated expression of MHC class II genes. Moreover, RCT led to the accumulation of monocytic myeloid-derived suppressor cells with increased pro-inflammatory features and CD16+ NK cells with a higher cytotoxic gene expression signature. However, subclusters of T cells showed no significant increase in the expression of cytotoxic features post-RCT. These results reveal the complex responses of the tumor ecosystem to RCT, providing evidence of activation of innate immunity and MHC-II upregulation in cervical cancer.

Construction of a CCL20-centered circadian-signature based prognostic model in cervical cancer

“…Although Hirotaka et al found that dietary consumption of Lactobacillus-derived exopolysaccharide induced CCR6 + CD8 + T cells by CCL20-secreting tumor cells [ 56 ], Wang et al also uncovered FOXO1 promoted the migration of M2 macrophages via CCL20 secretion in esophageal squamous cell carcinoma [ 57 ]. Besides, resently Liu et alrevealed a specific M2-like macrophages subtype with high CCL20 expression, which is associated with worse prognosis by single-cell analysis in CESC [ 58 ]. Besides, they proposed that CCL20 + macrrophges also expressed high levels of CXCL8, which is in accordance with our PPI analysis in TCGA-CESC as well [ 59 ].…”

Transdermal Transfersome Nanogels Control Hypertrophic Scar Formation via Synergy of Macrophage Phenotype‐Switching and Anti‐Fibrosis Effect

“…GO analysis demonstrated that the interleukin cytokines were the major molecular event altered in TA/Fu‐TS inhibiting inflammation (Figure 5E). [ 20 ] Therefore, TA/Fu‐TS could promote the macrophage phenotype‐switching, and inhibit inflammation by interleukin‐related pathways.…”

Targeting CD74-positive macrophages improves neoadjuvant therapy in cervical cancer as revealed by single-cell transcriptomics analysis

“…Specific subpopulations of cervical cancer, such as the HPV-reprogrammed keratinocyte subpopulation, were identified to provide evidence for tumor virus infection and cancer evolution 29 . The radiochemotherapy-induced innate immune activation and MHC-II upregulation in cervical cancer was also revealed by scRNA-seq 30 . Single-cell dissection of T cell subpopulation in cervical cancer tissues showed that targeting IDO1 and immune checkpoint inhibitors could improve the therapeutic efficacy 31 .…”