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Oncogenic CMTM6 drives M2a macrophages formation and fuels cervical cancer progression

Bo Yin1, Chun Chen2, Baoyou Huang1,3

  • 1Department of Gynecology, Shanghai Key Laboratory of Maternal Fetal Medicine, Shanghai Institute of Maternal-Fetal Medicine and Gynecologic Oncology, Shanghai First Maternity and Infant Hospital, School of Medicine, Tongji University, Shanghai, China.

Frontiers in Immunology
|August 5, 2025
PubMed
Abstract

Insights

Exosomal CMTM6 drives immune suppression in cervical cancer by promoting M2a macrophage polarization and activating the mTOR pathway. This CMTM6/CD206/CCL2 axis worsens prognosis and offers a potential therapeutic target for cervical cancer immunotherapy.

Area of Science:

  • Oncology
  • Immunology
  • Molecular Biology

Background:

  • CMTM6 (CKLF like MARVEL transmembrane member 6) is implicated in cancer progression.
  • Its role in cervical cancer (CC) and the tumor microenvironment (TME) is not well understood.
  • CMTM6 may contribute to an immunosuppressive TME.

Purpose of the Study:

  • To investigate the expression and function of CMTM6 in cervical cancer.
  • To determine CMTM6's impact on macrophage polarization and the tumor microenvironment.
  • To explore CMTM6 as a potential prognostic biomarker and therapeutic target in CC.

Main Methods:

  • In vitro assays and mouse xenograft models were used to study CMTM6 in CC cells.
  • Macrophage polarization (M2a) and mTOR signaling pathway activation were evaluated.
  • Exosome secretion and uptake by macrophages were analyzed.

Main Results:

  • CMTM6 is encapsulated in exosomes secreted by CC cells and taken up by macrophages.
  • Exosomal CMTM6 induces M2a macrophage polarization and immunosuppressive pathways.
  • CMTM6 presence correlates with increased macrophage infiltration and poor prognosis in CC.
  • Exosomal CMTM6 activates mTOR signaling in macrophages, increasing CCL2 secretion, promoting M2a polarization and metastasis.

Conclusions:

  • Exosomal CMTM6 is a key driver of immune suppression in cervical cancer.
  • The CMTM6/CD206/CCL2 axis is linked to increased risk and unfavorable prognosis in CC patients.
  • Exosomal CMTM6 shows potential as a prognostic biomarker and therapeutic target for CC immunotherapy.
Keywords:
CMTM6M2Acervical cancerexosomal CMTM6macrophage polarization

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