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<p>Esophageal squamous cell carcinoma (ESCC) is characterized by immune evasion and poor clinical outcomes. Autophagy has been implicated in tumor–immune interactions, but the molecular factors linking autophagy-associated processes to immune modulation in ESCC remain incompletely defined. We analyzed PSD3 expression in ESCC tissues and its association with prognosis and MHC-I–related molecules. Protein interactions were assessed by co-immunoprecipitation. Autophagy-associated marker changes, autophagic flux, total MHC-I protein levels, and immune cell infiltration were evaluated following PSD3 knockdown in murine and human ESCC models using Western blotting, tandem fluorescent LC3 reporter assays, immunohistochemistry, and single-cell RNA sequencing. Epistasis analysis was performed by silencing ATG7 following PSD3 knockdown. PSD3 was upregulated in ESCC and associated with unfavorable prognosis. PSD3 knockdown was accompanied by changes in autophagy-associated markers and reduced autophagosome abundance. In KYSE150 cells, tandem fluorescent mCherry–eGFP–LC3B analysis showed that PSD3 silencing impaired autophagic flux. PSD3 co-immunoprecipitated with ATG7, BAG3 and TBK1, supporting its association with autophagy-related protein complexes. PSD3 knockdown increased total MHC-I protein levels and was associated with enhanced immune cell infiltration in syngeneic tumor models. Furthermore, ATG7 silencing following PSD3 knockdown selectively restored HLA-E expression, while HLA-ABC and HLA-F showed no clearly distinguishable change. These findings support a working model in which PSD3 is linked to autophagy-associated immune modulation in ESCC. While additional studies are required to define pathway hierarchy and antigen-presentation function more directly, PSD3 emerges as a candidate molecular node for further mechanistic and translational investigation.</p>

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PSD3 links autophagic flux to MHC-I–associated immune modulation in esophageal squamous cell carcinoma

  • 期刊论文

  • 发表日期：

    2026年5月18日

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  • Shujuan Luo,
  • Aididar Nurbahati,
  • Bangwu Cai,
  • Hong Cui,
  • Tianyuan Peng,
  • Wei Wang,
  • Huifang Li,
  • Jiao Chen,
  • Qing Liu,
  • Xiaomei Lu,
  • Shutao Zheng

摘要

Esophageal squamous cell carcinoma (ESCC) is characterized by immune evasion and poor clinical outcomes. Autophagy has been implicated in tumor–immune interactions, but the molecular factors linking autophagy-associated processes to immune modulation in ESCC remain incompletely defined. We analyzed PSD3 expression in ESCC tissues and its association with prognosis and MHC-I–related molecules. Protein interactions were assessed by co-immunoprecipitation. Autophagy-associated marker changes, autophagic flux, total MHC-I protein levels, and immune cell infiltration were evaluated following PSD3 knockdown in murine and human ESCC models using Western blotting, tandem fluorescent LC3 reporter assays, immunohistochemistry, and single-cell RNA sequencing. Epistasis analysis was performed by silencing ATG7 following PSD3 knockdown. PSD3 was upregulated in ESCC and associated with unfavorable prognosis. PSD3 knockdown was accompanied by changes in autophagy-associated markers and reduced autophagosome abundance. In KYSE150 cells, tandem fluorescent mCherry–eGFP–LC3B analysis showed that PSD3 silencing impaired autophagic flux. PSD3 co-immunoprecipitated with ATG7, BAG3 and TBK1, supporting its association with autophagy-related protein complexes. PSD3 knockdown increased total MHC-I protein levels and was associated with enhanced immune cell infiltration in syngeneic tumor models. Furthermore, ATG7 silencing following PSD3 knockdown selectively restored HLA-E expression, while HLA-ABC and HLA-F showed no clearly distinguishable change. These findings support a working model in which PSD3 is linked to autophagy-associated immune modulation in ESCC. While additional studies are required to define pathway hierarchy and antigen-presentation function more directly, PSD3 emerges as a candidate molecular node for further mechanistic and translational investigation.