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Multiomic analysis of cervical squamous cell carcinoma identifies cellular ecosystems with biological and clinical

Junpeng Fan1,2, Funian Lu1,2, Tianyu Qin1,2

  • 1Department of Gynecological Oncology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.

Nature Genetics
|November 21, 2023
PubMed

Insights

Cervical cancer cells exist in distinct states impacting the tumor microenvironment. Understanding these states, like epithelial-immune (Epi-Imm), may improve immune-checkpoint blockade therapy response.

Area of Science:

  • Oncology
  • Immunology
  • Genomics

Background:

  • Cervical squamous cell carcinoma (CSCC) shows limited efficacy with immune-checkpoint blockade therapy.
  • Intratumoral heterogeneity significantly influences treatment outcomes in CSCC.

Purpose of the Study:

  • To create a high-resolution, spatially resolved map of intratumoral expression heterogeneity in CSCC.
  • To elucidate the distinct tumor immune microenvironments associated with different CSCC cellular states.

Main Methods:

  • Multiomic analysis including single-cell RNA sequencing, spatial transcriptomics, and spatial proteomics.
  • Integration of genetic and pharmacological perturbations to study cellular interactions.
  • Analysis of tumor samples from a cervical cancer clinical trial (NCT04516616).

Main Results:

  • Three distinct CSCC tumor states identified: epithelial-cytokeratin, epithelial-immune (Epi-Imm), and epithelial senescence.
  • Epithelial-cytokeratin tumors exhibit immune exclusion via cancer-associated fibroblast interactions and TGF-β signaling.
  • Epi-Imm tumors show malignant cell interactions with NK and T cells through interferon signaling.

Conclusions:

  • Neoadjuvant chemotherapy can induce a transition to the Epi-Imm state in CSCC.
  • The Epi-Imm state correlates with pathological complete remission after immune-checkpoint blockade.
  • Findings enhance understanding of CSCC cellular diversity and immune microenvironment interactions.

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