암세포 표면의 박테리아 막 성분 기능화에 기반한 대식세포 유도 면역치료 전략 = Macrophage-mediated immunotherapy strategy based on bacterial membrane component functionalization of the cancer cell surface

다국어 초록 (Multilingual Abstract)

Macrophages possess an inherent capacity to detect and remove aberrant cells, making them attractive agents for cell-based immunotherapy against cancer. Nonetheless, their innate tumor-killing functions, such as phagocytosis and inflammatory signaling, are often impeded in the immunosuppressive tumor microenvironment, diminishing overall therapeutic efficacy. Reinforcement of macrophage immune activity was achieved by functionalizing tumor cell membranes with bacterial pathogen-associated molecular patterns （PAMPs）, thereby restoring their responsiveness toward cancer cells. The resulting bacteria- like cancer cells retained strong immunostimulatory activity, leading to markedly increased macrophage-mediated phagocytosis of tumor cells and elevated secretion of inflammatory cytokines. In murine tumor models, intratumoral administration of these PAMP-decorated nanoparticles effectively suppressed tumor growth in a macrophage-dependent manner. Collectively, these results highlight a versatile macrophage-based immunotherapy strategy that transforms tumor cells into bacteria-like targets, thereby reprogramming macrophages within the tumor microenvironment to achieve potent antitumor responses.

목차 (Table of Contents)

• 1. Introduction 1
• 2. Materials and Methods 4
• 2.1. Cell culture and macrophage differentiation 4
• 2.2. Animals and ethical statement 5
• 2.3. Preparation of bacterial membrane extracts （BME） 5
• 2.4. Nitrite quantification （Griess assay） 6
• 2.5. Macrophage activation and cytokine analysis 7
• 2.6. Endocytosis inhibition assay 7
• 2.7. PRR pathway blockade 8
• 2.8. Surface charge adjustment and membrane association 8
• 2.9. Phagocytosis assay 9
• 2.10. Tumor models and treatment protocols 10
• 2.11. Tissue imaging and histology 10
• 3. Results and Discussion11
• 3.1. Macrophage activation through bacterial membrane extract–induced signaling pathways 11
• 3.2. BMEplus formulation enables rapid surface association with cancer cell membranes 16
• 3.3. Macrophage inflammatory and phagocytic responses toward bacteria mimicking cancer cells 20
• 3.4. In vivo therapeutic evaluation of BME formulations 23
• 4. Conclusions 26
• 5. References 27