American Association for Cancer Research
10780432ccr122199-sup-tab4.xlsx (9.22 kB)

Supplementary Table 4 from PD-L1 on Tumor Cells Is Induced in Ascites and Promotes Peritoneal Dissemination of Ovarian Cancer through CTL Dysfunction

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posted on 2023-03-31, 17:54 authored by Kaoru Abiko, Masaki Mandai, Junzo Hamanishi, Yumiko Yoshioka, Noriomi Matsumura, Tsukasa Baba, Ken Yamaguchi, Ryusuke Murakami, Ayaka Yamamoto, Budiman Kharma, Kenzo Kosaka, Ikuo Konishi

XLSX file - 63K, Table S4 shows FDR q value and FWER p value in the result of GSEA. Up-regulated genes in PD-L1 affected mouse CTLs and up-regulated genes in PD-1-signal-transmitted human CTLs show significant correlation, and so do the down-regulated genes.



Purpose: Ovarian cancer often progresses by disseminating to the peritoneal cavity, but how the tumor cells evade host immunity during this process is poorly understood. Programmed cell death 1 ligand 1 (PD-L1) is known to suppress immune system and to be expressed in cancer cells. The purpose of this study is to elucidate the function of PD-L1 in peritoneal dissemination.Experimental Design: Ovarian cancer cases were studied by microarray and immunohistochemistry. PD-L1 expression in mouse ovarian cancer cell line in various conditions was assessed by flow cytometry. PD-L1–overexpression cell line and PD-L1–depleted cell line were generated, and cytolysis by CTLs was analyzed, and alterations in CTLs were studied by means of timelapse and microarray. These cell lines were injected intraperitoneally to syngeneic immunocompetent mice.Results: Microarray and immunohistochemistry in human ovarian cancer revealed significant correlation between PD-L1 expression and peritoneal positive cytology. PD-L1 expression in mouse ovarian cancer cells was induced upon encountering lymphocytes in the course of peritoneal spread in vivo and coculture with lymphocytes in vitro. Tumor cell lysis by CTLs was attenuated when PD-L1 was overexpressed and promoted when it was silenced. PD-L1 overexpression inhibited gathering and degranulation of CTLs. Gene expression profile of CTLs caused by PD-L1–overexpressing ovarian cancer was associated with CTLs exhaustion. In mouse models, PD-L1 depletion resulted in inhibited tumor growth in the peritoneal cavity and prolonged survival.Conclusion: PD-L1 expression in tumor cell promotes peritoneal dissemination by repressing CTL function. PD-L1–targeted therapy is a promising strategy for preventing and treating peritoneal dissemination. Clin Cancer Res; 19(6); 1363–74. ©2012 AACR.