YO-PING LAILU-CHENG KUOBEEN-REN LINHUNG-JU LINLin, Chih-YuChih-YuLinChen, Yi-TingYi-TingChenHsiao, Pei-WenPei-WenHsiaoChang, Huan-TsungHuan-TsungChangPATRICK CHOW-IN KOChen, Hsiao-ChinHsiao-ChinChenChang, Hsiang-YuHsiang-YuChangLu, JeanJeanLuHONG-NERNG HOBETTY AN-YE WU-HSIEHKung, John TJohn TKungSHU-CHING CHEN2022-10-132022-10-132021-122399-3642https://scholars.lib.ntu.edu.tw/handle/123456789/623669CD28 is required for T cell activation as well as the generation of CD4+Foxp3+ Treg. It is unclear, however, how CD28 costimulation affects the development of CD8+ T cell suppressive function. Here, by use of Hepa1.6.gp33 in vitro killing assay and B16.gp33 tumor mouse model we demonstrate that CD28 engagement during TCR ligation prevents CD8+ T cells from becoming suppressive. Interestingly, our results showed that ectonucleotidase CD73 expression on CD8+ T cells is upregulated in the absence of CD28 costimulation. In both murine and human tumor-bearing hosts, CD73 is upregulated on CD28-CD8+ T cells that infiltrate the solid tumor. UPLC-MS/MS analysis revealed that CD8+ T cells activation without CD28 costimulation produces elevated levels of adenosine and that CD73 mediates its production. Adenosine receptor antagonists block CD73-mediated suppression. Our data support the notion that CD28 costimulation inhibits CD73 upregulation and thereby prevents CD8+ T cells from becoming suppressive. This study uncovers a previously unidentified role for CD28 costimulation in CD8+ T cell activation and suggests that the CD28 costimulatory pathway can be a potential target for cancer immunotherapy.enIN-VITRO; EXTRACELLULAR ADENOSINE; B-CELL; COSTIMULATION; CD73; LYMPHOCYTES; CD39; STIMULATION; PROMOTES; CANCER[SDGs]SDG3journal article10.1038/s42003-021-02119-9340119622-s2.0-85106061207WOS:000658813000002https://scholars.lib.ntu.edu.tw/handle/123456789/571027