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Published on: March 15, 2024
TRIM36 and CAMK2N2 regulate ferroptosis and antigen presentation in small cell lung cancer
Yifan Cai1,2,3, Shuang Zhu1,2,3, Honglin Wang4
1Cancer Center, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, China.
Abstract:
Small cell lung cancer (SCLC) is a highly aggressive tumor with poor prognosis. Ferroptosis is closely linked to tumor antigen presentation: it affects antigen presentation efficiency via immunostimulatory signals, while CD8+ T cell activation induced by antigen presentation promotes tumor cell ferroptosis by secreting IFNγ. This study used multi-omics analyses and machine learning to screen key genes, verified by in vitro/in vivo experiments. TRIM36 and CAMK2N2 were significantly upregulated in SCLC, negatively correlating with patient survival, effector memory CD8+ T cell infiltration, and tumor MHC I expression. They suppress SCLC antigen presentation via ferroptosis-dependent/independent mechanisms, limiting T cell function. TRIM36 and CAMK2N2 are promising SCLC biomarkers and therapeutic targets, providing clues to unravel ferroptosis-antigen presentation associations in tumor cells and optimize immunotherapeutic strategies.