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Updated: Dec 13, 2025

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MDMX phosphorylation-dependent p53 downregulation contributes to an immunosuppressive tumor microenvironment

Bing Wang1,2,3, Chuan-Bian Lim3, Jiawei Yan3

  • 1Key Laboratory of Space Radiobiology of Gansu Province & Key Laboratory of Heavy Ion Radiation Biology and Medicine of Chinese Academy of Sciences, Institute of Modern Physics, Chinese Academy of Sciences, Lanzhou, China.

Journal of Molecular Cell Biology
|July 25, 2020
PubMed

Insights

The tumor microenvironment (TME) plays a crucial role in cancer progression. This study reveals how targeting p53 in the TME can enhance anti-cancer therapy by restoring immune function.

Area of Science:

  • Oncology
  • Immunology
  • Molecular Biology

Background:

  • The tumor-suppressive role of p53 within the tumor microenvironment (TME) is understudied.
  • Understanding how tumors manipulate host p53 to create a pro-tumorigenic TME is critical.

Purpose of the Study:

  • To investigate how implanted tumor cells affect host p53 within the TME.
  • To explore the impact of p53 downregulation on immune cell activity and tumor progression.
  • To evaluate the therapeutic potential of modulating p53 activity in the TME.

Main Methods:

  • Utilized MdmxS314A mice as recipients for implanted tumor cells.
  • Analyzed p53 downregulation in peritumor cells induced by tumor cell-associated stress.
  • Assessed immune cell infiltration and macrophage polarization within the TME.
  • Investigated the effect of ablating MDMX-Ser314 phosphorylation on p53 levels and TME immunosuppression.

Main Results:

  • Tumor cells induced p53 downregulation in peritumor cells via MDMX-Ser314 phosphorylation.
  • This p53 decline resulted in an immunosuppressive TME with reduced immune cell infiltration and M1 macrophage polarization.
  • Ablating MDMX-Ser314 phosphorylation mitigated p53 decline, reduced immunosuppression, and delayed tumor growth.

Conclusions:

  • p53 plays a novel role in regulating the tumor immune microenvironment.
  • Restoring p53 activity within the TME presents a potential anticancer therapeutic strategy.
  • Targeting the MDMX-Ser314 phosphorylation pathway offers a means to modulate p53 and enhance anti-tumor immunity.
Keywords:
MDMXimmune cell infiltrationmacrophage polarizationp53tumor microenvironment

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