Các tế bào T điều hòa ở bệnh nhân ung thư đại trực tràng ức chế hoạt động miễn dịch chống khối u theo cách phụ thuộc COX-2

Springer Science and Business Media LLC - Tập 57 - Trang 813-821 - 2007
Sheraz Yaqub1,2, Karen Henjum1,2,3, Milada Mahic1,2, Frode L. Jahnsen4, Einar M. Aandahl1,2, Bjørn A. Bjørnbeth3, Kjetil Taskén1,2
1The Biotechnology Centre of Oslo, University of Oslo, Oslo, Norway
2Centre for Molecular Medicine Norway, Nordic EMBL Partnership, University of Oslo, Oslo, Norway
3Department of Gastroenterological Surgery, Ullevaal University Hospital, Oslo, Norway
4The Pathology Clinic, Rikshospitalet-Radiumhospitalet Medical Center, Oslo, Norway

Tóm tắt

Các tế bào T điều hòa tự nhiên (TR) ức chế các tế bào T tự phản ứng trong khi các tế bào TR thích nghi, được cảm ứng ở ngoại vi, đóng vai trò quan trọng trong các bệnh viêm mãn tính và ung thư. Nhiều nghiên cứu chỉ ra rằng các chất ức chế cyclooxygenase (COX) ngăn ngừa sự phát triển ung thư của các adenoma ruột già và trì hoãn sự tiến triển của bệnh ở những bệnh nhân bị ung thư đại trực tràng (CRC). Chúng tôi đã chỉ ra rằng các tế bào TR thích nghi biểu hiện COX-2 và sản xuất PGE2, điều này ức chế các tế bào T hiệu ứng theo cách có thể bị đảo ngược bởi các chất ức chế COX. Ở đây, chúng tôi chứng minh rằng bệnh nhân CRC có mức PGE2 cao trong máu ngoại vi, và các mẫu mô CRC cùng với các hạch bạch huyết dẫn dường như có số lượng tế bào TR FOXP3+ gia tăng. Việc loại bỏ các tế bào TR khỏi PBMC làm tăng cường các phản ứng tế bào T chống khối u đối với các peptide từ kháng nguyên phôi ung thư. Hơn nữa, chất ức chế COX indomethacin và thuốc đối kháng PKA loại I Rp-8-Br-cAMPS cải thiện đáng kể hoạt động miễn dịch chống khối u. Chúng tôi gợi ý rằng các tế bào TR thích nghi góp phần vào một môi trường vi mô ức chế miễn dịch trong CRC và ức chế các tế bào T hiệu ứng thông qua một cơ chế phụ thuộc COX-2–PGE2, từ đó tạo điều kiện cho sự phát triển của khối u. Các chiến lược điều trị nhắm vào các tế bào TR và con đường PGE2–cAMP có thể là những hướng nghiên cứu thú vị để tăng cường hoạt động miễn dịch chống khối u ở bệnh nhân CRC.

Từ khóa

#Tế bào T điều hòa #ung thư đại trực tràng #COX-2 #PGE2 #miễn dịch chống khối u

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