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Published on: May 30, 2025

Macrophage-derived long non-coding RNAs in cancer: pioneering targets for immune modulation and personalized therapy

Prasanna Srinivasan Ramalingam1, Md Sadique Hussain2, Yumna Khan3

  • 1Protein Engineering Lab, School of Biosciences and Technology, Vellore Institute of Technology, Vellore, Tamil Nadu, India.

Frontiers in Immunology
|May 14, 2026
PubMed

Insights

Macrophage-derived long non-coding RNAs (lncRNAs) play dual roles in cancer, with M2-derived lncRNAs promoting tumor growth and M1-derived lncRNAs suppressing it. These lncRNAs offer potential as cancer biomarkers and therapeutic targets.

Area of Science:

  • * Oncology
  • * Immunology
  • * Molecular Biology

Background:

  • * Long non-coding RNAs (lncRNAs) generated by macrophages are critical regulators of cancer progression, immune evasion, and therapeutic responses.
  • * Tumor-associated macrophages (TAMs) and their derived lncRNAs significantly influence the tumor microenvironment and cancer hallmarks.
  • * Understanding the distinct roles of M1 and M2 macrophage-derived lncRNAs is crucial for developing novel cancer immunotherapies.

Purpose of the Study:

  • * To investigate the multifaceted roles of lncRNAs from M1 and M2 macrophage subtypes in regulating tumor progression and immune responses.
  • * To explore the potential of macrophage-derived lncRNAs as diagnostic biomarkers and therapeutic targets in cancer immunotherapy.
  • * To highlight recent advancements in lncRNA research, including single-cell RNA sequencing and CRISPR-based functional studies, for improved cancer diagnostics and treatment optimization.

Main Methods:

  • * Review and analysis of existing literature on macrophage-derived lncRNAs in cancer.
  • * Investigation of specific lncRNAs (e.g., H19, AFAP1-AS1, CRNDE, HOTTIP, NBR2) and their functions.
  • * Integration of findings from single-cell RNA sequencing and CRISPR-based functional studies.

Main Results:

  • * M2-derived lncRNAs (H19, AFAP1-AS1, CRNDE) promote tumor proliferation, metastasis, and chemoresistance.
  • * M1-derived lncRNAs (HOTTIP, NBR2) exhibit tumor-suppressive functions by enhancing inflammation and inhibiting epithelial-mesenchymal transition.
  • * Macrophage-derived lncRNAs modulate immune control through macrophage polarization, cytokine production, and immune checkpoint regulation.

Conclusions:

  • * Macrophage-derived lncRNAs exhibit distinct oncogenic or tumor-suppressive roles dependent on macrophage polarization (M1 vs. M2).
  • * These lncRNAs are pivotal in regulating cancer immunity, microenvironment, and treatment sensitivity, offering significant potential for personalized cancer immunotherapy.
  • * Emerging technologies are enhancing the identification and functional characterization of lncRNAs, paving the way for novel diagnostic and therapeutic strategies in oncology.
Keywords:
immune modulationimmunotherapymacrophagespersonalized medicinetumor microenvironmenttumor-associated macrophages

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