2435 - Targeting Protein Kinase CK2 to Reprogram Phospholipid Metabolism and Enhance the Efficacy of Radioimmunotherapy in Lung Cancer
Presenter(s)
Q. Luo1,2, S. You3, L. Chen4, and R. Meng5; 1Cancer Center, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Wuhan, China, 2Hubei Key Laboratory of Precision Radiation Oncology, Wuhan, China, Wuhan, Wuhan, China, 31Cancer Center, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China; 2Hubei Key Laboratory of Precision Radiation Oncology, Wuhan, China., Wuhan, Wuhan, China, 41Cancer Center, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China; 2Hubei Key Laboratory of Precision Radiation Oncology, Wuhan, China., Wuhan, China, 5Cancer Center, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, China
Purpose/Objective(s): Resistance to tumor therapy is a major cause of tumor treatment failure. Evasion of anti-tumor immune effects by tumor cells through the PD-1/PD-L1 axis has been identified as an important factor contributing to resistance to radioimmunotherapy in lung cancer patients. Protein kinase CK2 has been shown to mediate almost all malignant phenotypes of tumors, and previous studies have confirmed that protein kinase CK2 plays an important role in both radiotherapy resistance and immune resistance. Consequently, targeting protein kinase CK2 has emerged as a promising target for radioimmunosensitization. The objective of this study was to elucidate the specific mechanism between protein kinase CK2 and radioimmunity effects in lung cancer, and to verify the feasibility of targeting protein kinase CK2 to promote radioimmunotherapy in lung cancer.
Materials/Methods: The correlation between protein kinase CK2 and the efficacy of immunotherapy after radiotherapy for lung cancer was explored through bioinformatics. Using a mouse subcutaneous tumor model, the role and immune mechanism of targeting protein kinase CK2 to promote radioimmunotherapy for lung cancer were explored through flow cytometry. The relationship between protein kinase CK2 and the metabolism of lung cancer cells was explored through non - targeted lipid metabolomics. The specific mechanism of CK2 regulating phospholipid metabolism was explored through RNA - seq. The changes in protein expression levels of molecules related to this topic were explored through WB.
Results: The overexpression of protein kinase CK2 in lung cancer has been identified. Targeting protein kinase CK2 enhances the radioimmunotherapy effect in lung cancer. The specific mechanism is that targeting protein kinase CK2 regulates the expression of LPCAT1 protein, thereby regulating phospholipid metabolism to inhibit the expression of PD - L1 in lung cancer cells and further modulating the radioimmunotherapy effect of lung cancer cells. In addition, the combination of targeting protein kinase CK2 and radioimmunotherapy has shown effective antitumor effects against Lewis mouse subcutaneous tumors.
Conclusion: Our findings indicate that protein kinase CK2 plays a significant role in the regulation of PD-L1 expression in lung cancer cells. Targeting protein kinase CK2 has been shown to enhance radioimmunity effects in lung cancer. The combination of targeted protein kinase CK2 with radioimmunotherapy is a promising therapeutic modality.