A research team led by Prof. Ki-Young Lee at the College of Medicine, Sungkyunkwan University, has uncovered a previously unrecognized tumor-intrinsic role of the immune checkpoint molecule PD-L1, providing new mechanistic insight into lung cancer progression.
PD-L1 (Programmed death-ligand 1) has been widely known for its role in helping tumors evade immune surveillance by suppressing anti-tumor immune responses. However, emerging evidence suggests that PD-L1 may also regulate intracellular signaling pathways within cancer cells. By integrating transcriptomic analyses of patient-derived non-small cell lung cancer (NSCLC) datasets with functional and molecular experiments, Prof. Lee’s research team demonstrated that PD-L1 acts as a critical regulator of autophagy and metastasis-related signaling networks within tumor cells.
Using CRISPR-Cas9-mediated gene editing and protein interaction analyses, the researchers identified a novel molecular mechanism in which PD-L1 directly regulates autophagy signaling. Importantly, PD-L1 depletion in lung cancer models resulted in: reduced cell proliferation, decreased migration and colony-forming capacity, and suppressed tumor growth and metastasis in xenograft models. These findings demonstrate that tumor-intrinsic PD-L1 plays a functional role in cancer progression beyond its canonical immune regulatory activity. Prof. Lee’s research group plans to further expand multi-omics-based cancer signaling research and translational precision medicine platforms to strengthen global research competitiveness.
This research was supported by the Ministry of Science and ICT and the National Research Foundation of Korea (MRC and Mid-career Researcher Programs). The study was published online on February 18, 2026, in the international journal Experimental Hematology & Oncology (Impact Factor 13.5, top 5.6% in JCR).
Experimental Hematology and Oncology
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