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May 2, 2026Frontiers in Immunology1 citationsOpen Access

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

PRPrasanna Srinivasan RamalingamMHMd Sadique HussainYKYumna Khan

Key Points

  • This research aims to explore the roles of macrophage-derived long non-coding RNAs (lncRNAs) in cancer biology and therapy.
  • Investigated lncRNAs from M1 and M2 macrophage subtypes regarding tumor progression and immune modulation.
  • Utilized single-cell RNA sequencing and CRISPR-based functional studies to identify lncRNA targets.
  • Analyzed the influence of lncRNAs on tumor proliferation, metastasis, and chemoresistance.
  • M2-derived lncRNAs, such as H19, promoted tumor proliferation and chemoresistance, while M1-derived lncRNAs exhibited tumor-suppressive effects.
  • Macrophage-derived lncRNAs regulated immune checkpoints and cytokine production, influencing immune responses in cancer.
  • Identified new lncRNA targets that enhance diagnostics and therapeutic strategies for personalized cancer immunotherapy.

Abstract

Generated from macrophages, long non-coding RNAs (lncRNAs) are increasingly recognized as imperative in influencing cancer immune evasion, microenvironment alteration, and therapy sensitivity. Together with tumor-associated macrophages (TAMs), this detailed investigation investigates the several roles of lncRNAs derived from M1 and M2 macrophage subtypes in regulating tumor progression. In contrast to the cancer-promoting effect of M2-based derived lncRNAs, such as H19, AFAP1-AS1, and CRNDE, which stimulate tumor proliferation, metastases, and chemoresistance through a variety of cascades, M1-based derived lncRNAs, such as HOTTIP and NBR2, exhibit tumor-suppressive roles in augmenting inflammatory signals and inhibiting epithelial-mesenchymal transition. Other than their involvement in the development of cancer, macrophage-derived lncRNAs have important immune control effects based on macrophage polarization, cytokine production, and immune checkpoints. Recent progress in single-cell RNA sequencing and the CRISPR-based functional studies also now provides new lncRNA targets and improved accuracy of diagnostics and optimization of therapy approaches. It marks a new step in personalized cancer immunotherapy: our research focuses on the possibilities of macrophage-derived lncRNAs as biomarkers and treatment options.

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Cite This Study

Ramalingam et al. (2026) studied this question.

synapsesocial.com/papers/69f5939871405d493affeaf9https://doi.org/10.3389/fimmu.2026.1711686
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