DataVXAdvanced SciencePaper
journal article·2025-09Open access

SMYD3 Promotes Immune Evasion in Clear Cell Renal Cell Carcinoma via SREBP1‐Mediated Transactivation of CD47

Zhengfang Liu, Xiumei Zhao, Maolin Zang, Huiyang Yuan, Xin Qin, Xiaofeng Li, Shuo Zhao, Ruirong Tan, Keqiang Yan, Li Liu, Yidong Fan, Ning Zhang, Benkang Shi, Bo Han, Shouzhen Chen

Advanced Science· Volume 12· Issue 34
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Abstract

Abstract Cancer cell‐intrinsic features (e.g., genetic aberrations and dysregulation of signaling pathways) play pivotal roles in orchestrating the composition and functional state of the immune landscape, which in turn impact tumor progression and response to immunotherapy. Here, it is discovered that dysregulation of cancer cell‐intrinsic SET and MYND domain‐containing protein 3 (SMYD3) leads to the orchestration of an immunosuppressive microenvironment and the impairment of responses to PD‐1 blockade by reprogramming the infiltration of immune cells in the tumor microenvironment of clear cell renal cell carcinoma (ccRCC). SMYD3 cooperates with Sp1 to transcriptionally promote sterol regulatory element‐binding protein 1 (SREBP1) expression by modifying H3‐K4 di‐/trimethylation and consequently activating the transcription of CD47. CD47, a bridge between innate and adaptive immunity, acts as the downstream effector molecule of the SMYD3 signal to promote the infiltration of T helper 2 (Th2) cells, protecting renal cancer cells from immune attack. In summary, the critical role of the cancer cell‐intrinsic SMYD3‐SREBP1‐CD47 axis is elucidated in regulating the immune microenvironment in ccRCC and provides a potential therapeutic strategy to manipulate the tumor immune milieu in favor of antitumor immunity.
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Research context

OpenAlex topics: Phagocytosis and Immune Regulation · Cancer Immunotherapy and Biomarkers · Ferroptosis and cancer prognosis

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

Affiliations

Thoracic Surgery Department Shandong Cancer Hospital and Institute Shandong First Medical University and Shandong Academy of Medical Science Jinan 250117 China

Department of Urology Qilu Hospital of Shandong University Jinan 2500112 China

Department of Pathology Qilu Hospital of Shandong University Jinan 250012 China

Department of Hematology The Second Hospital of Shandong University Jinan 250033 China

Department of Urology The First Affiliated Hospital of Shandong First Medical University & Shandong Provincial Qianfoshan Hospital Shandong Medicine and Health Key Laboratory of Organ Transplantation and Nephrosis Shandong Institute of Nephrology Jinan 250013 China

Translational Chinese Medicine Key Laboratory of Sichuan Province Sichuan Institute for Translational Chinese Medicine Sichuan Academy of Chinese Medicine Sciences Chengdu 610042 China

School of Nursing Beijing University of Chinese Medicine Beijing 100191 China

Department of Breast Surgery General Surgery Qilu Hospital of Shandong University Jinan 250012 China

Department of Pathology Peking University People's Hospital Beijing 100044 China

Funding

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

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