Single‐cell dissection of cervical cancer reveals key subsets of the tumor immune microenvironment

Abstract

The tumor microenvironment (TME) directly determines patients' outcomes and therapeutic efficiencies. An in‐depth understanding of the TME is required to improve the prognosis of patients with cervical cancer (CC). This study conducted single‐cell RNA and TCR sequencing of six‐paired tumors and adjacent normal tissues to map the CC immune landscape. T and NK cells were highly enriched in the tumor area and transitioned from cytotoxic to exhaustion phenotypes. Our analyses suggest that cytotoxic large‐clone T cells are critical effectors in the antitumor response. This study also revealed tumor‐specific germinal center B cells associated with tertiary lymphoid structures. A high‐germinal center B cell proportion in patients with CC is predictive of improved clinical outcomes and is associated with elevated hormonal immune responses. We depicted an immune‐excluded stromal landscape and established a joint model of tumor and stromal cells to predict CC patients' prognosis. The study revealed tumor ecosystem subsets linked to antitumor response or prognosis in the TME and provides information for future combinational immunotherapy. image Single‐cell level evaluation of the composition of malignant, immune, and stromal cells in the tumor microenvironment of cervical cancer (CC) determines critical subsets of immune response and prognosis. Single‐cell and immune repertoire analysis of CC and adjacent normal tissue highlights critical immune and stromal clusters. T cells are mostly exhausted in CC, while large clones are more prone to cytotoxic immune responses. The presence of tertiary lymphoid structures and germinal center response in CC tumors links to B‐cell–mediated anti‐tumor response. Co‐occurrence analysis of epithelial and stromal subsets provides a promising prognostic model for patients with CC.