Lai W.-Y.Huang B.-T.Wang J.-W.Lin P.-Y.PAN-CHYR YANG2020-12-022020-12-0220162162-2531https://www.scopus.com/inward/record.uri?eid=2-s2.0-85015613333&doi=10.1038%2fmtna.2016.102&partnerID=40&md5=0176a22a130a1c5188035703e55936ffhttps://scholars.lib.ntu.edu.tw/handle/123456789/523491The PD-1/PD-L1 axis is a major pathway involved in tumor immune evasion. Here, we report the novel PD-L1 antagonizing DNA aptamer (aptPD-L1) and demonstrate an integrated pipeline that expedites therapeutic aptamer development. Aptamer can exert antibody-mimic functions and is advantageous over antibody for its chemically synthetic nature, low immunogenicity, and efficient tissue penetration. Our results showed that aptPD-L1 blocked the binding between human PD-1 and PD-L1. Experiments using murine models showed that aptPD-L1 promoted in vitro lymphocyte proliferation and suppressed in vivo tumor growth without the induction of observable liver or renal toxicity. Analyses on the aptPD-L1-treated tumors further revealed elevated levels of infiltrating CD4+ and CD8+ T cells, intratumoral IL-2, TNF-α, interferon (IFN)-γ and the C-X-C motif chemokines, CXCL9 and CXCL10. The CD8+ T cells in the aptPD-L1-treated tumors had higher CXCR3 expression level compared to the random-sequence oligonucleotides-treated ones. Besides, the length and density of CD31+ intratumoral microvessels were significantly decreased in the aptPD-L1 treatment group. Collectively, our data suggested that aptPD-L1 helps T cell function restoration and modifies tumor microenvironment. These chemokines might orchestrate together to attract more T cells into the tumor tissues to form the positive amplification loop against tumor growth, indicating the translational potential of aptPD-L1 in cancer immunotherapy. ? 2016 Official journal of the American Society of Gene & Cell Therapyaptamer; immunotherapy; PD-1; PD-L1; tumor microenvironment[SDGs]SDG3alpha chemokine; aptamer; atezolizumab; CD31 antigen; chemokine receptor CXCR3; CXCL9 chemokine; gamma interferon; gamma interferon inducible protein 10; interleukin 2; programmed death 1 ligand 1; tumor necrosis factor; A-549 cell line; animal experiment; animal model; antineoplastic activity; Article; cancer immunotherapy; cancer inhibition; CD4+ T lymphocyte; CD8+ T lymphocyte; controlled study; hop92 cancer cell line; human; human cell; in vitro study; liver toxicity; lung cancer cell line; lymphocyte proliferation; molecular docking; mouse; nephrotoxicity; nonhuman; priority journal; protein expression; protein protein interaction; protein targeting; sequence alignment; tumor growth; tumor microenvironment; tumor volumejournal article10.1038/mtna.2016.1022-s2.0-85015613333