Journal
JOURNAL OF TRANSLATIONAL MEDICINE
Volume 20, Issue 1, Pages -Publisher
BMC
DOI: 10.1186/s12967-022-03574-6
Keywords
Cervical cancer; SPOP; Multiplex immunofluorescence; PD-1; PD-L1 axis; CXCL16; CXCR6 axis
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Funding
- Beijing Kanghua Foundation for the Development of Traditional Chinese and Western Medicine [KH-2021-LLZX-037]
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This study reveals that SPOP plays a promoting role in cervical cancer metastasis by inhibiting the immune microenvironment through promoting the separation of PD-1 from PD-L1, leading to worse prognosis for patients.
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.
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