摘要
The T cell co-stimulatory molecule OX40 and its cognate ligand OX40 L have attracted broad research interest as a therapeutic target in T cell-mediated diseases.Accumulating preclinical evidence highlights the therapeutic efficacy of both agonist and blockade of the OX40-OX40 L interaction.Despite this progress,many questions about the immuno-modulator roles of OX40 on T cell function remain unanswered.In this review we summarize the impact of the OX40-OX40 L interaction on T cell subsets,including Th1,Th2,Th9,Th17,Th22,Treg,Tfh,and CD8+T cells,to gain a comprehensive understanding of anti-OX40 mAb-based therapies.The potential therapeutic application of the OX40-OX40 L interaction in autoimmunity diseases and cancer immunotherapy are further discussed;OX40-OX40 L blockade may ameliorate autoantigen-specific T cell responses and reduce immune activity in autoimmunity diseases.We also explore the rationale of targeting OX40-OX40 L interactions in cancer immunotherapy.Ligation of OX40 with targeted agonist anti-OX40 mAbs conveys activating signals to T cells.When combined with other therapeutic treatments,such as anti-PD-1 or anti-CTLA-4 blockade,cytokines,chemotherapy,or radiotherapy,the anti-tumor activity of agonist anti-OX40 treatment will be further enhanced.These data collectively suggest great potential for OX40-mediated therapies.
The T cell co-stimulatory molecule OX40 and its cognate ligand OX40 L have attracted broad research interest as a therapeutic target in T cell-mediated diseases.Accumulating preclinical evidence highlights the therapeutic efficacy of both agonist and blockade of the OX40-OX40 L interaction.Despite this progress,many questions about the immuno-modulator roles of OX40 on T cell function remain unanswered.In this review we summarize the impact of the OX40-OX40 L interaction on T cell subsets,including Th1,Th2,Th9,Th17,Th22,Treg,Tfh,and CD8+T cells,to gain a comprehensive understanding of anti-OX40 mAb-based therapies.The potential therapeutic application of the OX40-OX40 L interaction in autoimmunity diseases and cancer immunotherapy are further discussed;OX40-OX40 L blockade may ameliorate autoantigen-specific T cell responses and reduce immune activity in autoimmunity diseases.We also explore the rationale of targeting OX40-OX40 L interactions in cancer immunotherapy.Ligation of OX40 with targeted agonist anti-OX40 mAbs conveys activating signals to T cells.When combined with other therapeutic treatments,such as anti-PD-1 or anti-CTLA-4 blockade,cytokines,chemotherapy,or radiotherapy,the anti-tumor activity of agonist anti-OX40 treatment will be further enhanced.These data collectively suggest great potential for OX40-mediated therapies.
基金
supported by the National Mitural Science Foundation of China(Nos.81872824 and 81690261).
作者简介
Corresponding authors:Zhirong Zhang,Tel.:+862885501566,fax:+862885501615.E-mail addresses:zrzzl@vip.sina.com;Corresponding authors:Ling Zhang,E-mail addresses:femcivrogner@outlook.com
