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

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.