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MicroRNA-targeted reprogramming of CD8+ T cells against cancer
Yuchen Mao1,2, Yujin Liu2, Kaiyan Jing2
1Department of Oncology, The First Affiliated Hospital, Jiangxi Medical College, Nanchang University, Nanchang, Jiangxi, China.
Frontiers in Immunology
|May 11, 2026
Summary
MicroRNAs (miRNAs) are key regulators in the communication between CD8+ T cells and tumor cells. Understanding these miRNA roles in the tumor microenvironment (TME) can advance precision immunotherapy.
Area of Science:
- Immunology
- Molecular Biology
- Oncology
Background:
- The tumor microenvironment (TME) is characterized by complex interactions between immune cells and tumor cells.
- MicroRNAs (miRNAs) are small non-coding RNAs that play crucial roles in regulating gene expression and cellular processes.
- CD8+ T cells are critical cytotoxic lymphocytes involved in anti-tumor immunity, but their function can be suppressed within the TME.
Purpose of the Study:
- To review and synthesize the current understanding of miRNA involvement in the bidirectional crosstalk between CD8+ T cells and tumor cells.
- To elucidate the mechanisms by which miRNAs modulate CD8+ T cell function and tumor cell behavior within the TME.
- To identify pan-cancer and tissue-specific miRNA functions and discuss their therapeutic potential.
Main Methods:
- Scoping review methodology was employed to systematically identify and analyze relevant literature.
- The review focused on studies investigating the role of specific miRNAs in CD8+ T cell-tumor cell interactions.
- Analysis included mechanisms of miRNA regulation, immune checkpoint modulation, metabolic reprogramming, and exosomal miRNA transfer.
Main Results:
- Specific miRNAs (e.g., miR-155, miR-340-5p) critically regulate CD8+ T cell functions, including immune checkpoints (PD-1/PD-L1), metabolism, and epigenetics.
- CD8+ T cells can influence tumor cells through exosomal transfer of miRNAs (e.g., miR-765).
- Both conserved (e.g., PD-1/PD-L1 regulation) and cancer-specific (e.g., miR-143 in melanoma) miRNA roles were identified.
Conclusions:
- miRNAs are central mediators of the intricate crosstalk between CD8+ T cells and tumor cells within the immunosuppressive TME.
- Targeting specific miRNAs or their delivery systems holds promise for developing novel combination therapies and precision immunotherapies.
- Further research into miRNA-mediated mechanisms and delivery strategies is essential for clinical translation.
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