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In Vitro Assay to Study Tumor-macrophage Interaction
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m6A RNA modification in tumor-associated macrophages: emerging roles in cancer immunity

Xi Chen1,2, Shanrui Pu3, Kun Lian1,2

  • 1NHC Key Laboratory of Drug Addiction Medicine, Kunming Medical University, Kunming, China.

Frontiers in Immunology
|October 20, 2025
PubMed

Insights

N6-methyladenosine (m6A) modification regulates tumor-associated macrophages (TAMs), influencing cancer immunity and treatment response. Targeting the m6A-TAM axis offers potential for novel cancer therapies.

Area of Science:

  • Epigenetics
  • Immunology
  • Cancer Biology

Background:

  • N6-methyladenosine (m6A) is a key post-transcriptional regulator of gene expression.
  • Tumor-associated macrophages (TAMs) are crucial players in the tumor immune microenvironment, impacting cancer progression and therapeutic outcomes.

Purpose of the Study:

  • To review the regulatory roles and mechanisms of m6A modification in TAM differentiation, polarization, and function.
  • To discuss the implications of m6A in TAM biology for anti-tumor immunity and immunotherapy resistance.
  • To explore therapeutic strategies targeting the m6A-TAM axis in cancer treatment.

Main Methods:

  • Literature review of recent studies on m6A modification and TAMs.
  • Analysis of m6A's impact on transcript stability, translation, and decay in TAMs.
  • Discussion of clinical relevance and therapeutic potential.

Main Results:

  • m6A dynamically regulates TAM phenotypes (M1/M2 balance) by controlling transcripts involved in inflammation, metabolism, and immune checkpoints.
  • Dysregulation of m6A machinery in TAMs is associated with suppressed anti-tumor immunity and immunotherapy resistance.
  • m6A modification is a critical determinant of TAM function within the tumor immune microenvironment.

Conclusions:

  • m6A modification plays a significant role in shaping TAM biology and influencing cancer immunity.
  • Targeting the m6A-TAM axis presents a promising therapeutic avenue for enhancing anti-tumor responses and overcoming immunotherapy resistance.
  • Further research into the m6A-TAM axis is warranted to develop effective cancer treatments.
Keywords:
YTHDF2cancer immunotherapym6A RNA modificationtumor microenvironmenttumor-associated macrophages

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