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Immunoregulatory roles of post-translational modifications in colorectal cancer: mechanisms and therapeutic

Xinyue Liang1, Jinhong Yao2, Wenbo Jiao3

  • 1Departments of Hematology, The First Hospital of Jilin University, Changchun, Jilin, 130021, China.

Cellular and Molecular Life Sciences : CMLS
|December 8, 2025
PubMed

Insights

Post-translational modifications (PTMs) significantly impact colorectal cancer (CRC) immunity and immunotherapy effectiveness. Understanding PTMs offers new strategies to enhance antitumor responses and overcome treatment resistance in CRC patients.

Area of Science:

  • Oncology
  • Immunology
  • Biochemistry

Background:

  • Colorectal cancer (CRC) is a major global health concern, with tumor immune evasion hindering effective immunotherapy.
  • Post-translational modifications (PTMs) regulate protein function and critically influence tumor immunogenicity and the tumor immune microenvironment.

Purpose of the Study:

  • To comprehensively review how PTMs modulate immune processes in CRC.
  • To highlight the role of PTMs in T cell exhaustion, macrophage polarization, and immune checkpoint regulation.
  • To discuss PTMs' impact on immunotherapy response and resistance, and explore PTM-targeted strategies.

Main Methods:

  • Literature review of PTMs in colorectal cancer immunology.
  • Analysis of PTM-mediated mechanisms affecting antigen presentation, immune cell infiltration, and immune checkpoints.
  • Examination of PTMs' influence on therapeutic outcomes and resistance to immunotherapies.

Main Results:

  • PTMs profoundly affect key immune functions in CRC, including antigen presentation and immune cell infiltration.
  • PTMs regulate T cell exhaustion, macrophage polarization, and immunosuppressive cytokine networks within the tumor microenvironment.
  • PTMs play a crucial role in determining response and resistance to immune checkpoint blockade and adoptive cell therapies.

Conclusions:

  • PTMs are critical regulators of the tumor immune microenvironment in CRC.
  • Targeting PTMs presents a promising avenue for enhancing antitumor immunity and overcoming immunotherapy resistance.
  • Advances in multi-omics and proteomics will accelerate the discovery of PTM biomarkers and therapeutic targets for CRC immunotherapy.
Keywords:
Immune checkpoint blockadeMacrophage polarizationPhosphorylationT cell exhaustionUbiquitination

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