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RKIP and tumor immune evasion: Remodeling the immunosuppressive tumor microenvironment
Evagelia Skouradaki1, Giasemi Eptaminitaki1, Evagelia Kirio1
1Laboratory of Experimental Oncology, Division of Surgery, School of Medicine, University of Crete, 71003 Heraklion, Greece.
Biochimica Et Biophysica Acta. Reviews on Cancer
|October 21, 2025
Summary
Raf-1 Kinase Inhibitor Protein (RKIP) acts as a metastasis suppressor and influences the tumor immune microenvironment. RKIP downregulation promotes immune evasion, but restoring it may enhance anti-tumor immunity and immunotherapy effectiveness.
Area of Science:
- Oncology
- Immunology
- Molecular Biology
Background:
- Raf-1 Kinase Inhibitor Protein (RKIP) is recognized for its role in suppressing metastasis.
- Emerging evidence highlights RKIP's dual function as an immunomodulatory molecule impacting the tumor immune microenvironment (TME).
Purpose of the Study:
- To explore RKIP's influence on immune surveillance and its interactions within the TME.
- To discuss RKIP's role in immune cell recruitment, polarization, and its impact on immune evasion.
Main Methods:
- Literature review of RKIP's interactions with signaling pathways and cellular components of the TME.
- Analysis of RKIP's effects on immune cell dynamics, cytokine profiles, and effector cell infiltration.
Main Results:
- RKIP downregulation correlates with increased immune evasion, altered cytokine profiles, and reduced effector immune cell infiltration.
- RKIP supports type I interferon signaling and antigen presentation, crucial for anti-tumor immunity.
Conclusions:
- Loss of RKIP contributes to an immunosuppressive, pro-metastatic TME.
- Regulating RKIP expression can reprogram the TME towards an immunoprotected state, enhancing immunotherapy efficacy.
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