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SPOP promotes cervical cancer progression by inducing the movement of PD-1 away from PD-L1 in spatial localization

Jiangchun Wu1,2, Yong Wu1,2, Qinhao Guo1,2

  • 1Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, 200032, China.

Journal of Translational Medicine
|August 30, 2022
PubMed
Abstract

Insights

SPOP protein promotes cervical cancer metastasis by disrupting PD-1 and PD-L1 interaction, leading to immune suppression and poorer patient survival outcomes.

Area of Science:

  • Oncology
  • Cancer Biology
  • Immunology

Background:

  • Metastasis remains a significant challenge in cervical cancer (CC) treatment.
  • The precise mechanisms of SPOP's involvement in CC metastasis require further investigation.

Purpose of the Study:

  • To elucidate the role and mechanism of SPOP in cervical cancer metastasis.
  • To investigate the association between SPOP expression and patient survival in CC.

Main Methods:

  • Proteomic sequencing and SPOP immunohistochemistry (IHC) on CC patient samples.
  • In vitro and in vivo experiments to assess SPOP's effect on CC proliferation and metastasis.
  • Multiplex immunofluorescence (m-IF) and HALO analysis to explore the underlying mechanism.

Main Results:

  • SPOP is upregulated in CC with lymph node metastasis and correlates with worse patient outcomes (OS and RFS).
  • SPOP enhances CC proliferation and metastasis in vitro and in vivo.
  • SPOP promotes CC metastasis by facilitating the spatial separation of PD-1 from PD-L1, inducing immune tolerance.

Conclusions:

  • SPOP promotes pelvic lymph node metastasis in cervical cancer by impairing the immune microenvironment.
  • SPOP-induced disruption of PD-1/PD-L1 interaction leads to immune suppression and negatively impacts overall and relapse-free survival in CC patients.
Keywords:
CXCL16/CXCR6 axisCervical cancerMultiplex immunofluorescencePD-1/PD-L1 axisSPOP

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