PD-1 Làm Giảm Chức Năng Của Các Tế Bào Dendritic Xâm Nhập Khối U Buồng Trứng Bằng Cách Vô Hiệu Hóa NF-κB
Tóm tắt
Trục tín hiệu miễn dịch PD-1:PD-L1 điều hòa sự ức chế miễn dịch khối u phụ thuộc tế bào T. Gần đây, sự biểu hiện PD-1 được phát hiện tăng cao trên các tế bào dendritic myeloid (CD11c+CD11b+CD8−CD209a+) của chuột và (CD1c+CD19−) của người xâm nhập khối u (TIDC), một loại tế bào miễn dịch bẩm sinh cũng liên quan đến việc thoát khỏi miễn dịch. Tuy nhiên, còn rất ít kiến thức về cách mà PD-1 điều chỉnh các tế bào miễn dịch bẩm sinh. Trong nghiên cứu này, chúng tôi đã kiểm tra vai trò của PD-1 trong các TIDC được lấy từ chuột mang khối u buồng trứng. Tương tự như các tế bào lympho, biểu hiện PD-1 trên TIDC liên quan đến sự biểu hiện của protein thích ứng SHP-2, vốn tín hiệu đến NF-κB; tuy nhiên, trái ngược với vai trò của nó ở tế bào lympho, chúng tôi nhận thấy rằng biểu hiện của PD-1 trên TIDC đã làm tê liệt một cách liên tục sự hoạt hóa NF-κB. Các cuộc điều tra cơ chế sâu hơn cho thấy PD-1 đã chặn sự phóng thích cytokine phụ thuộc NF-κB theo cách phụ thuộc vào SHP-2. Ngược lại, việc ức chế sự trình diện kháng nguyên trung gian NF-κB do PD-1 gây ra độc lập với SHP-2. Tổng thể, những phát hiện của chúng tôi cho thấy PD-1 hoạt động theo một cách khác biệt trong các tế bào miễn dịch bẩm sinh so với các tế bào miễn dịch thích nghi, khuyến khích các nghiên cứu sâu hơn về các con đường tín hiệu được kiểm soát bởi trung gian chính này trong việc thoát khỏi miễn dịch ở ung thư.
Từ khóa
#PD-1 #NF-κB #tế bào dendritic #miễn dịch khối u #thoát khỏi miễn dịchTài liệu tham khảo
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