Single-cell transcriptomics unveils multifaceted immune heterogeneity in early-onset versus late-onset cervical cancer

World J Surg Oncol. 2025 Jan 14;23(1):12. doi: 10.1186/s12957-025-03654-z.

Abstract

Early-onset (EOCC) and late-onset cervical cancers (LOCC) represent two clinically distinct subtypes, each defined by unique clinical manifestations and therapeutic responses. However, their immunological profiles remain poorly explored. Herein, we analyzed single-cell transcriptomic data from 4 EOCC and 4 LOCC samples to compare their immune architectures. Epithelial cells in EOCC exhibited a notable dual immunological phenotype, characterized by immune-suppressive properties driven by elevated CXCL production, alongside immune-stimulatory features linked to heightened HLA molecule expression. CD4 + and CD8 + T cells in LOCC demonstrated a heightened activation state, while NK cells exhibited diminished cytotoxicity. Macrophages in LOCC displayed enhanced polarization towards both M1 and M2 phenotypes, along with dendritic cells showing augmented antigen-presenting capacity. Regarding cancer-associated fibroblasts (CAFs), EOCC was enriched with inflammatory CAFs, whereas LOCC harbored a higher proportion of antigen-presenting CAFs. These findings reveal the multifaceted immune heterogeneity between EOCC and LOCC, underscoring the imperative for age-tailored immunotherapeutic strategies.

Keywords: Age; Cervical cancer; Immune heterogeneity; Single-cell RNA sequencing.

MeSH terms

  • Age of Onset
  • CD8-Positive T-Lymphocytes / immunology
  • Cancer-Associated Fibroblasts / immunology
  • Cancer-Associated Fibroblasts / metabolism
  • Cancer-Associated Fibroblasts / pathology
  • Dendritic Cells / immunology
  • Female
  • Gene Expression Profiling
  • Humans
  • Killer Cells, Natural / immunology
  • Macrophages / immunology
  • Macrophages / metabolism
  • Prognosis
  • Single-Cell Analysis* / methods
  • Transcriptome
  • Tumor Microenvironment / immunology
  • Uterine Cervical Neoplasms* / genetics
  • Uterine Cervical Neoplasms* / immunology
  • Uterine Cervical Neoplasms* / pathology