Non-small cell lung cancer(NSCLC)is a leading cause of cancer-related mortality worldwide1-3.While radioimmuno-therapy shows promise in boosting antitumor immunity,the clinical outcomes have been inconsistent4 and are...Non-small cell lung cancer(NSCLC)is a leading cause of cancer-related mortality worldwide1-3.While radioimmuno-therapy shows promise in boosting antitumor immunity,the clinical outcomes have been inconsistent4 and are often lim-ited by the immunosuppressive tumor microenvironment(TME).Cyclooxygenase(COX)-2 and the COX-2 downstream product,prostaglandin E2(PGE2),are increasingly implicated in immune escape5,6 but the impact on radioimmunother-apy efficacy has not been explored.TCF1-expressing CD8+T cells demonstrate defining functional properties of progeni-tor-exhausted T cells,including clonal expansion through self-renewal capacity and multipotent differentiation toward terminal effector phenotypes,while maintaining long-term persistence critical for sustaining antitumor immunity7-9.Given the central role in anti-tumor immune maintenance,TCF1+CD8+T cells are likely critical to radioimmunotherapy efficacy10.The role of COX-2 inhibition in enhancing the effi-cacy of radioimmunotherapy efficacy in NSCLC was investi-gated in the current study.展开更多
基金funded by the National Natural Science Foundation of China(Grant Nos.82030082 and 82272845)the Natural Science Foundation of Shandong Province(Grant No.ZR2023LZL001).
文摘Non-small cell lung cancer(NSCLC)is a leading cause of cancer-related mortality worldwide1-3.While radioimmuno-therapy shows promise in boosting antitumor immunity,the clinical outcomes have been inconsistent4 and are often lim-ited by the immunosuppressive tumor microenvironment(TME).Cyclooxygenase(COX)-2 and the COX-2 downstream product,prostaglandin E2(PGE2),are increasingly implicated in immune escape5,6 but the impact on radioimmunother-apy efficacy has not been explored.TCF1-expressing CD8+T cells demonstrate defining functional properties of progeni-tor-exhausted T cells,including clonal expansion through self-renewal capacity and multipotent differentiation toward terminal effector phenotypes,while maintaining long-term persistence critical for sustaining antitumor immunity7-9.Given the central role in anti-tumor immune maintenance,TCF1+CD8+T cells are likely critical to radioimmunotherapy efficacy10.The role of COX-2 inhibition in enhancing the effi-cacy of radioimmunotherapy efficacy in NSCLC was investi-gated in the current study.
