2. Academic Validation
  3. SPOP promotes cervical cancer progression by inducing the movement of PD-1 away from PD-L1 in spatial localization

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

  • J Transl Med. 2022 Aug 30;20(1):384. doi: 10.1186/s12967-022-03574-6.
Jiangchun Wu  # 1 2,  Yong Wu  # 1 2,  Qinhao Guo  # 1 2,  Siyu Chen 1 2,  Simin Wang 1 2,  Xiaohua Wu  # 3 4,  Jun Zhu  # 5 6,  Xingzhu Ju  # 7 8
Affiliations

Affiliations

  • 1 Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, 200032, China.
  • 2 Department of Gynecologic Oncology, Fudan University Shanghai Cancer Center, Fudan University, Shanghai, 200032, People's Republic of China.
  • 3 Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, 200032, China. wu.xh@fudan.edu.cn.
  • 4 Department of Gynecologic Oncology, Fudan University Shanghai Cancer Center, Fudan University, Shanghai, 200032, People's Republic of China. wu.xh@fudan.edu.cn.
  • 5 Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, 200032, China. joelchu88@qq.com.
  • 6 Department of Gynecologic Oncology, Fudan University Shanghai Cancer Center, Fudan University, Shanghai, 200032, People's Republic of China. joelchu88@qq.com.
  • 7 Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, 200032, China. xingzhu_ju@163.com.
  • 8 Department of Gynecologic Oncology, Fudan University Shanghai Cancer Center, Fudan University, Shanghai, 200032, People's Republic of China. xingzhu_ju@163.com.
  • # Contributed equally.
PMID: 36042498 DOI: 10.1186/s12967-022-03574-6
Abstract

Background: Metastasis is a major obstacle in the treatment of cervical Cancer (CC), and SPOP-mediated regulatory effects are involved in metastasis. However, the mechanisms have not been fully elucidated.

Methods: Proteomic Sequencing and SPOP immunohistochemistry (IHC) were performed for the pelvic lymph node (pLN)-positive and non-pLN groups of CC patients. The corresponding patients were stratified by SPOP expression level for overall survival (OS) and relapse-free survival (RFS) analysis. In vitro and in vivo tests were conducted to verify the causal relationship between SPOP expression and CC metastasis. Multiplex immunofluorescence (m-IF) and the HALO system were used to analyse the mechanism, which was further verified by in vitro experiments.

Results: SPOP is upregulated in CC with pLN metastasis and negatively associated with patient outcome. In vitro and in vivo, SPOP promotes CC proliferation and metastasis. According to m-IF and HALO analysis, SPOP may promote CC metastasis by promoting the separation of PD-1 from PD-L1. Finally, it was further verified that SPOP can achieve immune tolerance by promoting the movement of PD-1 away from PD-L1 in spatial location and function.

Conclusion: This study shows that SPOP can inhibit the immune microenvironment by promoting the movement of PD-1 away from PD-L1, thereby promoting pLN metastasis of CC and resulting in worse OS and RFS.

Keywords

CXCL16/CXCR6 axis; Cervical cancer; Multiplex immunofluorescence; PD-1/PD-L1 axis; SPOP.

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