Study on the immunoregulatory role of SMYD3 in the breast tumor microenvironment

목차 (Table of Contents)

• ABSTRACT ⅰii
• Ⅰ. Introduction 1
• 1.1 Immunotherapy in breast cancer 1
• 1.2 Epigenetic regulation of the tumor microenvironment 3
• 1.3 SMYD3 as an epigenetic regulator of tumor immunity 4
• Ⅱ. Materials and methods 6
• Ⅲ. Results 17
• 3.1 SMYD3 promotes breast tumor progression in a T cell–dependent manner 17
• 3.2 SMYD3 restricts T cell infiltration during mid and late stages of tumor progression 18
• 3.3 SMYD3 impairs T cell functional states predominantly at the early stage of tumor progression 20
• 3.4 SMYD3 upregulates IFN-γ driven PD-L1 on the cancer cell surface to suppress CD8⁺ T cell activity 22
• 3.5 SMYD3 differentially modulates the efficacy of PD-L1 and PD-1 blockade 24
• 3.6 Suppression of CD8+ T cell infiltration by SMYD3 is recovered by anti-PD-L1 26
• 3.7 Tumor cell-intrinsic PD-L1 mediates SMYD3-induced cellular signaling 28
• Ⅳ. Figure 31
• Ⅴ. Discussion 47
• Ⅵ. References 58