精准医学杂志 (Aug 2023)
EFFECT OF TARGETED INHIBITION OF Myc ON IMMUNOGENICITY OF LEWIS LUNG CARCINOMA WHOLE-CELL VACCINE IN MICE
Abstract
Objective To prepare a whole-cell vaccine for murine Lewis lung carcinoma (LLC), and to investigate the role of this vaccine in enhancing the anti-LLC ability of immune system in C57BL/6N mice. Methods TCGA database was used to analyze the changes in the infiltration level of immune cells within human lung adenocarcinoma (LUAD) tissue in the context of MYC amplification, and the optimal duration of ultraviolet irradiation was explored for the preparation of LLC whole-cell vaccine. A mouse model was used to assess the effect of LLC whole-cell vaccine with targeted inhibition of Myc on resistance to LLC. Results In human LUAD tissue samples, compared with the low N-MYC expression group, the high N-MYC expression group had a significant reduction in the infiltration abundance of activated CD4+ memory T cells and activated NK cells (W=28 233,27 990,P<0.05) and a significant increase in the infiltration abundance of Tregs cells (W=36 074,P<0.05). The mouse LLC cells treated by an inhibitor completely lost their activity after 15 minutes of ultraviolet irradiation, and there were significant reductions in the expression levels of c-Myc, N-Myc, and PD-L1 within LLC cells (t=6.26-13.51,P<0.05). In the mouse model experiment, compared with the Irra group, the Irra treatment group showed a reduction in tumor growth rate and an increase in survival time. In addition, the Irra treatment group had significant increases in CD3+CD8+/CD3+ ratio in the spleen and tumor and the serum levels of the cytokines tumor necrosis factor-α and interferon gamma (F=54.83-381.10,P<0.05). Conclusion The LLC whole-cell vaccine is successfully prepared in this study. In the mouse experiment, vaccination of the LLC whole-cell vaccine with targeted inhibition of Myc can enhance the ability of the immune system to attack LLC, thereby reducing tumor growth rate and prolonging survival time.
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