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journal article·2026-01Open access

tRNA‐Derived Fragment tRF‐22 Promotes Immunosuppression by Inhibiting HnRNPAB Ubiquitination in Esophageal Squamous Cell Carcinoma

Ling Pan, Xin Qin, Li Gong, Haining Liu, Bo Cheng, Jing Wang, Yajie Hu, Lingxing Zeng, Yiping Wang, Qingxu Song, Yufeng Cheng

Advanced Science· Volume 13· Issue 1
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Source abstract

Abstract

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 tRNA GlnCTG/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.
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Research context

OpenAlex topics: RNA modifications and cancer · interferon and immune responses · Ubiquitin and proteasome pathways

SciVX discovery tags are terminology-based. OpenAlex topics are source-provided classifications.

Affiliations

Department of Radiation Oncology Qilu Hospital of Shandong University Cheeloo College of Medicine Shandong University Jinan 250012 China

Shandong Provincial Key Laboratory of Malignant Tumor Precision Treatment Jinan 250012 China

Shandong Provincial Engineering Research Center for Tumor Precision Treatment Jinan 250012 China

Department of Urology Qilu Hospital of Shandong University Cheeloo College of Medicine Shandong University Jinan 250012 China

Department of Organ Transplantation Qilu Hospital of Shandong University Cheeloo College of Medicine Shandong University Jinan 250012 China

Department of Urologic Oncology The First Affiliated Hospital of USTC Division of Life Sciences and Medicine University of Science and Technology of China Hefei 230001 China

State Key Laboratory of Oncology in South China and Guangdong Provincial Clinical Research Center for Cancer Sun Yat‐sen University Cancer Center Guangzhou 510060 China

Funding

National Natural Science Foundation of China · Taishan Scholar Foundation of Shandong Province · Natural Science Foundation of Shandong Province

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