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<p>Small extracellular vesicles (sEVs), carrying PD-L1, have been implicated in immune evasion and tumor progression. However, understanding how PD-L1 sEVs are secreted still needs to be improved. We found that the secretion dynamics of PD-L1 sEVs is similar to that of other sEVs. Intracellular calcium and the associated downstream PKC signaling plays pivotal roles in releasing PD-L1 sEVs in non-small cell lung cancer cells (NSCLC). Particularly, we observed that knocking down PKCα has profound impacts on PD-L1 sEVs secretion, especially in the resting state and in the activated state, when induced by an intracellular calcium rise. Furthermore, our study revealed that PKCα regulates PD-L1 expression and PD-L1 sEVs secretion by influencing STAT1 phosphorylation and nuclear translocation in a p53-dependent manner. Notably, p53 can regulate STAT1 phosphorylation and nuclear localization, but it does not affect PKCα expression. This suggests that PKCα plays a significant role in regulating PD-L1 expression. Our findings suggest that targeting PKCα to modulate PD-L1 dynamics in NSCLC may be a promising therapeutic strategy to enhance the efficacy of immunotherapeutic interventions.</p>

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PKCα regulates the secretion of PDL1-carrying small extracellular vesicles in a p53-dependent manner

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2025年1月14日

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  • Ren Zhang,
  • Weilin Liao,
  • Xi Chen,
  • Junyi Wang,
  • Jiaqi Li,
  • Geer Chen,
  • Weiyu Wu,
  • Xiaoxuan Wang,
  • Yao Zhang,
  • Ziyu Chen,
  • Xiaoyu Zhu,
  • Zicong Lin,
  • Yizhun Zhu,
  • Lijuan Ma,
  • Haijie Yu

摘要

Small extracellular vesicles (sEVs), carrying PD-L1, have been implicated in immune evasion and tumor progression. However, understanding how PD-L1 sEVs are secreted still needs to be improved. We found that the secretion dynamics of PD-L1 sEVs is similar to that of other sEVs. Intracellular calcium and the associated downstream PKC signaling plays pivotal roles in releasing PD-L1 sEVs in non-small cell lung cancer cells (NSCLC). Particularly, we observed that knocking down PKCα has profound impacts on PD-L1 sEVs secretion, especially in the resting state and in the activated state, when induced by an intracellular calcium rise. Furthermore, our study revealed that PKCα regulates PD-L1 expression and PD-L1 sEVs secretion by influencing STAT1 phosphorylation and nuclear translocation in a p53-dependent manner. Notably, p53 can regulate STAT1 phosphorylation and nuclear localization, but it does not affect PKCα expression. This suggests that PKCα plays a significant role in regulating PD-L1 expression. Our findings suggest that targeting PKCα to modulate PD-L1 dynamics in NSCLC may be a promising therapeutic strategy to enhance the efficacy of immunotherapeutic interventions.