MP39-15 YAP EXPRESSION PLAYS IMPORTANT ROLES IN MALIGNANT AGGRESSIVENESS BY REGULATING THE INFILTRATION OF CD57 + NATURAL KILLER CELLS, CD68 + MACROPHAGES, AND MAST CELLS AND THE EXPRESSION OF VEGF-A AND PD-L1 IN CLEAR CELL RENAL CELL CARCINOMA

Abstract

You have accessJournal of UrologyKidney Cancer: Basic Research & Pathophysiology I (MP39)1 Sep 2021MP39-15 YAP EXPRESSION PLAYS IMPORTANT ROLES IN MALIGNANT AGGRESSIVENESS BY REGULATING THE INFILTRATION OF CD57+ NATURAL KILLER CELLS, CD68+ MACROPHAGES, AND MAST CELLS AND THE EXPRESSION OF VEGF-A AND PD-L1 IN CLEAR CELL RENAL CELL CARCINOMA Kojiro Ohba, Yasuyoshi Miyata, Junki Harada, Tsuyoshi Matsuda, Tsubasa Kondo, Asato Otsubo, Yuta Mukae, Hidenori Ito, Hiroki Kurata, Kensuke Mitsunari, Hideki Sakai, Tomohiro Matsuo, and Yasushi Mochizuki Kojiro OhbaKojiro Ohba More articles by this author , Yasuyoshi MiyataYasuyoshi Miyata More articles by this author , Junki HaradaJunki Harada More articles by this author , Tsuyoshi MatsudaTsuyoshi Matsuda More articles by this author , Tsubasa KondoTsubasa Kondo More articles by this author , Asato OtsuboAsato Otsubo More articles by this author , Yuta MukaeYuta Mukae More articles by this author , Hidenori ItoHidenori Ito More articles by this author , Hiroki KurataHiroki Kurata More articles by this author , Kensuke MitsunariKensuke Mitsunari More articles by this author , Hideki SakaiHideki Sakai More articles by this author , Tomohiro MatsuoTomohiro Matsuo More articles by this author , and Yasushi MochizukiYasushi Mochizuki More articles by this author View All Author Informationhttps://doi.org/10.1097/JU.0000000000002054.15AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract INTRODUCTION AND OBJECTIVE: The Hippo signalling pathway is known as a critical regulator of malignant aggressiveness, and Yes-associated protein (YAP) is the most important downstream effector in this pathway. Although, YAP has pro-oncogenic activities, its detailed mechanisms are not fully understood. Recently, YAP has been reported to play important roles in tumour immunity, by regulating tumour-infiltrating lymphocytes and vascular endothelial growth factor (VEGF)-A and programmed cell death ligand 1 (PD-L1). However, the relationships between YAP expression, the densities of macrophages, natural killer (NK) cells, and mast cells; and VEGF-A and PD-L1 expression in human clear cell renal cell carcinoma (ccRCC) are not clear. METHODS: In 157 ccRCC tissues, the expression levels of YAP and VEGF-A were evaluated by immunohistochemistry, according to the percentage of positively stained cells and staining intensity. The densities of CD57+ NK cells, CD68+ macrophages, and mast cells were calculated as the number of positively stained cells per high-power field (HPF). All examinations were performed using immunohistochemical staining. RESULTS: Positive expression of YAP was significantly associated with high tumor grade, high pT stage, the presence of metastasis, and poor cause-specific survival in patients with ccRCC (p<0.001). CD57+ NK cell density was significantly lower (p<0.001) in YAP-positive tissues (mean±SD, 22.1 ± 8.0/HPF) than in YAP-negative tissues (33.1 ± 8.4/HPF). In contrast, CD68+ macrophage density was significantly higher (p<0.001) in YAP-positive tissues (44.2±14.5/HPF) than that in YAP-negative tissues (29.3±9.8/HPF). Similarly, YAP expression was positively correlated with mast cell density (p<0.001). However, H-scores of PD-L1 were significantly lower (p<0.001) in YAP-positive tissues (6.6±9.6) than in YAP-negative tissues (3.1±6.0). In addition, a similar positive correlation was detected between YAP expression and VEGF-A expression (p<0.001). CD57+ NK cell, CD68+ macrophage, and mast cell density and VEGF-A and PD-L1 expression were all significantly associated with pathological features. CONCLUSIONS: YAP expression was positively associated with tumour growth, invasion, and metastasis by stimulating the infiltration of CD58+ macrophages and mast cells into cancer tissues; increasing the expression of VEGF-A and PD-L1 in cancer cells; and suppressing the infiltration of CD57+ NK cells. Source of Funding: None © 2021 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 206Issue Supplement 3September 2021Page: e710-e710 Advertisement Copyright & Permissions© 2021 by American Urological Association Education and Research, Inc.MetricsAuthor Information Kojiro Ohba More articles by this author Yasuyoshi Miyata More articles by this author Junki Harada More articles by this author Tsuyoshi Matsuda More articles by this author Tsubasa Kondo More articles by this author Asato Otsubo More articles by this author Yuta Mukae More articles by this author Hidenori Ito More articles by this author Hiroki Kurata More articles by this author Kensuke Mitsunari More articles by this author Hideki Sakai More articles by this author Tomohiro Matsuo More articles by this author Yasushi Mochizuki More articles by this author Expand All Advertisement Loading ...