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

The EMBO Journal, 2023 · DOI: 10.15252/embj.2022110757 · Published: July 10, 2023

Simple Explanation

This study used single-cell RNA and TCR sequencing to map the immune landscape of cervical cancer. T and NK cells were found to be highly enriched in the tumor area. These cells transitioned from cytotoxic to exhaustion phenotypes. The research also identified tumor-specific germinal center B cells associated with tertiary lymphoid structures. A high germinal center B cell proportion is predictive of improved clinical outcomes. This is associated with elevated hormonal immune responses. The study established a joint model of tumor and stromal cells to predict cervical cancer patients’ prognosis. The research provides information for future combinational immunotherapy.

Study Duration

Not specified

Participants

Six-paired tumors and adjacent normal tissues

Evidence Level

Not specified

Key Findings

1
Cytotoxic large-clone T cells are critical effectors in the antitumor response.
2
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.
3
The study revealed tumor ecosystem subsets linked to antitumor response or prognosis in the TME.

Research Summary

This study conducted single-cell RNA and TCR repertoire sequencing of primary CC tissues and adjacent normal tissues to decode the heterogeneity of the TME. The intra- and inter-tumoral heterogeneity of cancer cells was revealed, and POSTN+ cells were identified as a potential-early invasive subtype. Finally, we described the distinct phenotypes of CAFs and endothelial cells harbored in the tumor region and established a joint model that could segment patients with differential epithelial-stromal co-occurrence patterns and prognosis.

Practical Implications

Immunotherapy Targets

The identification of cytotoxic large-clone T cells and tumor-specific B cell responses provides potential targets for immunotherapy.

Prognostic Markers

The association of high-germinal center B cell proportion with improved clinical outcomes suggests its potential as a prognostic marker.

Combination Therapy Strategies

The study's insights into the tumor microenvironment can inform the development of future combinational immunotherapy strategies.

Study Limitations

1
The study could not explore TME variations across HPV subtypes and histology due to the small sample size.
2
The use of biopsy forceps in tissue collection and a lack of cell sorting resulted in inadequate GCB cell numbers for further analysis.
3
The epitopes collected in VDJdb database were limited to E7 protein, which might lead to a severe underestimation of HPV-specific cells.

Your Feedback

Was this summary helpful?

Back to Oncology