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
  • 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. [email protected].
  • 4. Department of Gynecologic Oncology, Fudan University Shanghai Cancer Center, Fudan University, Shanghai, 200032, People's Republic of China. [email protected].
  • 5. Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, 200032, China. [email protected].
  • 6. Department of Gynecologic Oncology, Fudan University Shanghai Cancer Center, Fudan University, Shanghai, 200032, People's Republic of China. [email protected].
  • 7. Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, 200032, China. [email protected].
  • 8. Department of Gynecologic Oncology, Fudan University Shanghai Cancer Center, Fudan University, Shanghai, 200032, People's Republic of China. [email protected].
  • # 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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