Related Experiment Video
Updated: May 3, 2026
An In Vitro Assay to Detect tRNA-Isopentenyl Transferase Activity
Published on: October 8, 2018
tRNA-Derived Fragment tRF-22 Promotes Immunosuppression by Inhibiting HnRNPAB Ubiquitination in Esophageal Squamous
Ling Pan1,2,3, Xin Qin4, Li Gong1,2,3
1Department of Radiation Oncology, Qilu Hospital of Shandong University, Cheeloo College of Medicine, Shandong University, Jinan, 250012, China.
Abstract:
Small proportions of patients with esophageal squamous cell carcinoma (ESCC) benefit from immune checkpoint blockade therapy, making it urgent to identify factors that limit its effectiveness. It is found that tRF-22, a small RNA derived from tRNAGlnCTG/TTG, promotes an immunosuppressive tumor microenvironment. High tRF-22 expression is associated with worse prognosis in ESCC. tRF-22 shapes immunosuppression by increasing polymorphonuclear myeloid-derived suppressor cells (PMN-MDSCs) infiltration and suppressing CD8+ T cells. Mechanistically, it binds to Lys91 on hnRNPAB, inhibiting its ubiquitination by TRIM25, leading to the stabilization of hnRNPAB, which activates TGFB2 transcription. Accumulated TGFβ2 promotes MDSCs generation to drive immunosuppression in ESCC. Using tRF-22 antagomir or TGFβ signaling blockade in combination with anti-PD1 therapy enhances immune response and reduces tumor growth. Overall, a tRF-22-hnRNPAB-TGFβ2-PMN-MDSCs-CD8+ T cell pathway is identified that drives immunosuppression and tumor growth. Targeting tRF-22 may be a promising strategy to improve immunotherapy efficacy in ESCC.
Insights
A small RNA called tRF-22 promotes an immunosuppressive tumor microenvironment in esophageal squamous cell carcinoma (ESCC), hindering immunotherapy. Targeting tRF-22 may improve treatment effectiveness for ESCC patients.
Area of Science:
- Oncology
- Molecular Biology
- Immunology
Background:
- Immune checkpoint blockade therapy shows limited efficacy in esophageal squamous cell carcinoma (ESCC).
- Identifying factors limiting immunotherapy response in ESCC is crucial.
- A novel small RNA, tRF-22, is implicated in promoting an immunosuppressive tumor microenvironment.
Purpose of the Study:
- To investigate the role of tRF-22 in ESCC immunosuppression.
- To elucidate the molecular mechanisms by which tRF-22 drives tumor growth.
- To evaluate therapeutic strategies targeting the tRF-22 pathway.
Main Methods:
- Analysis of tRF-22 expression in ESCC patient samples.
- Investigating the impact of tRF-22 on immune cell infiltration (PMN-MDSCs, CD8+ T cells).
- Elucidating the molecular interaction between tRF-22, hnRNPAB, TRIM25, and TGFB2.
- Evaluating the efficacy of tRF-22 antagomir and TGFβ signaling blockade in combination with anti-PD1 therapy in preclinical models.
Main Results:
- High tRF-22 expression correlates with worse prognosis in ESCC.
- tRF-22 enhances polymorphonuclear myeloid-derived suppressor cells (PMN-MDSCs) infiltration and suppresses CD8+ T cells.
- tRF-22 stabilizes hnRNPAB by inhibiting its ubiquitination, leading to increased TGFB2 transcription.
- Combined therapy with tRF-22 antagomir or TGFβ blockade and anti-PD1 therapy improved immune response and reduced tumor growth.
Conclusions:
- A tRF-22-hnRNPAB-TGFβ2-PMN-MDSCs-CD8+ T cell pathway drives immunosuppression and tumor growth in ESCC.
- Targeting tRF-22 represents a potential strategy to enhance immunotherapy efficacy in ESCC.
- Modulating this pathway offers a promising therapeutic avenue for improving outcomes in esophageal squamous cell carcinoma.
Related Concept Videos
01:00Enzyme-linked Receptors
Neurotrophin (NT) receptors are a family of RTKs, including trkA, trkB, and trkC (tropomyosin-related kinase) receptors. TrkA is specific for nerve growth factor (NGF), neurotrophin-6, and neurotrophin-7. TrkB binds...
03:18Non-LTR Retrotransposons