Targeted　therapy　produces　objective　responses　in　bladder　cancer　patients,　although　the　responses　can　be　short.　Meanwhile,　response　rates　to　immune　therapy　are　lower,　but　the　effects　are　more　durable.　Based　on　these　findings,　it　was　hypothesized　that　urothelial　carcinoma　associated　1　(UCA1)-targeted　therapy　could　synergize　with　programmed　cell　death　1　(PD-1)　blockade　to　enhance　antitumor　activity.　To　test　this　hypothesis,　the　effects　of　CRISPR-Cas9　targeting　of　UCA1　and　PD-1　were　assessed　in　vitro　and　in　vivo.　It　was　found　that　gRNA/cas9-targeted　UCA1　induced　apoptosis　of　5637　bladder　cancer　cells,　whereas　PD-1　gene　knockout　could　be　achieved　by　electroporation　of　gRNA/cas9　targeting　PD-1,　as　detected　by　polymerase　chain　reaction.　In　5637　cell-xenografted　humanized　SCID　mice,　stimulation　with　CRISPR-Cas9　systems,　immune　phenotypes,　and　cytokine　expression　of　human　dendritic　cells　(DCs)　was　detected　by　flow　cytometry,　and　polymerase　chain　reaction,　respectively.　The　results　of　these　assays　suggested　that　the　gRNA/cas9　treatment　upregulated　expression　of　CD80,　CD83,　and　CD86　and　significantly　increased　interleukin　(IL)-6,　IL-12,　and　IL-23　and　tumor　necrosis　factor　alpha　mRNA　levels.　Co-administration　of　anti-PD-1　and　anti-UCA1　treatment　suppressed　tumor　growth　and　markedly　improved　survival　of　5637　xenografted　mice.　Additionally,　the　combination　treatment　increased　interferon　gamma　production　by　T　cells　that　subsequently　enhanced　the　expression　of　Th1-associated　immune-stimulating　genes　to　reduce　transcription　of　regulatory/suppressive　immune　genes　and　reshape　the　tumor　microenvironment　from　an　immunosuppressive　to　a　stimulatory　state.　Finally,　anti-UCA1　treatment　was　shown　to　induce　interferon　gamma-dependent　programmed　cell　death　ligand　1　expression　within　5637　xenograft　tumors　in　vivo.　Together,　these　results　demonstrate　potent　synergistic　effects　of　a　combination　therapy　using　LncRNA　UCA1-targeted　therapy　and　immune　checkpoint　blockade　of　PD-1,　thus　supporting　the　translational　potential　of　this　combination　strategy　for　clinical　treatment　of　bladder　cancer.