Cargando…

A systematic CRISPR screen reveals an IL-20/IL20RA-mediated immune crosstalk to prevent the ovarian cancer metastasis

Transcoelomic spread of cancer cells across the peritoneal cavity occurs in most initially diagnosed ovarian cancer (OC) patients and accounts for most cancer-related death. However, how OC cells interact with peritoneal stromal cells to evade the immune surveillance remains largely unexplored. Here...

Descripción completa

Detalles Bibliográficos
Autores principales: Li, Jia, Qin, Xuan, Shi, Jie, Wang, Xiaoshuang, Li, Tong, Xu, Mengyao, Chen, Xiaosu, Zhao, Yujia, Han, Jiahao, Piao, Yongjun, Zhang, Wenwen, Qu, Pengpeng, Wang, Longlong, Xiang, Rong, Shi, Yi
Formato: Online Artículo Texto
Lenguaje:English
Publicado: eLife Sciences Publications, Ltd 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8195602/
https://www.ncbi.nlm.nih.gov/pubmed/34114949
http://dx.doi.org/10.7554/eLife.66222
_version_ 1783706525417603072
author Li, Jia
Qin, Xuan
Shi, Jie
Wang, Xiaoshuang
Li, Tong
Xu, Mengyao
Chen, Xiaosu
Zhao, Yujia
Han, Jiahao
Piao, Yongjun
Zhang, Wenwen
Qu, Pengpeng
Wang, Longlong
Xiang, Rong
Shi, Yi
author_facet Li, Jia
Qin, Xuan
Shi, Jie
Wang, Xiaoshuang
Li, Tong
Xu, Mengyao
Chen, Xiaosu
Zhao, Yujia
Han, Jiahao
Piao, Yongjun
Zhang, Wenwen
Qu, Pengpeng
Wang, Longlong
Xiang, Rong
Shi, Yi
author_sort Li, Jia
collection PubMed
description Transcoelomic spread of cancer cells across the peritoneal cavity occurs in most initially diagnosed ovarian cancer (OC) patients and accounts for most cancer-related death. However, how OC cells interact with peritoneal stromal cells to evade the immune surveillance remains largely unexplored. Here, through an in vivo genome-wide CRISPR/Cas9 screen, we identified IL20RA, which decreased dramatically in OC patients during peritoneal metastasis, as a key factor preventing the transcoelomic metastasis of OC. Reconstitution of IL20RA in highly metastatic OC cells greatly suppresses the transcoelomic metastasis. OC cells, when disseminate into the peritoneal cavity, greatly induce peritoneum mesothelial cells to express IL-20 and IL-24, which in turn activate the IL20RA downstream signaling in OC cells to produce mature IL-18, eventually resulting in the polarization of macrophages into the M1-like subtype to clear the cancer cells. Thus, we show an IL-20/IL20RA-mediated crosstalk between OC and mesothelial cells that supports a metastasis-repressing immune microenvironment.
format Online
Article
Text
id pubmed-8195602
institution National Center for Biotechnology Information
language English
publishDate 2021
publisher eLife Sciences Publications, Ltd
record_format MEDLINE/PubMed
spelling pubmed-81956022021-06-14 A systematic CRISPR screen reveals an IL-20/IL20RA-mediated immune crosstalk to prevent the ovarian cancer metastasis Li, Jia Qin, Xuan Shi, Jie Wang, Xiaoshuang Li, Tong Xu, Mengyao Chen, Xiaosu Zhao, Yujia Han, Jiahao Piao, Yongjun Zhang, Wenwen Qu, Pengpeng Wang, Longlong Xiang, Rong Shi, Yi eLife Cancer Biology Transcoelomic spread of cancer cells across the peritoneal cavity occurs in most initially diagnosed ovarian cancer (OC) patients and accounts for most cancer-related death. However, how OC cells interact with peritoneal stromal cells to evade the immune surveillance remains largely unexplored. Here, through an in vivo genome-wide CRISPR/Cas9 screen, we identified IL20RA, which decreased dramatically in OC patients during peritoneal metastasis, as a key factor preventing the transcoelomic metastasis of OC. Reconstitution of IL20RA in highly metastatic OC cells greatly suppresses the transcoelomic metastasis. OC cells, when disseminate into the peritoneal cavity, greatly induce peritoneum mesothelial cells to express IL-20 and IL-24, which in turn activate the IL20RA downstream signaling in OC cells to produce mature IL-18, eventually resulting in the polarization of macrophages into the M1-like subtype to clear the cancer cells. Thus, we show an IL-20/IL20RA-mediated crosstalk between OC and mesothelial cells that supports a metastasis-repressing immune microenvironment. eLife Sciences Publications, Ltd 2021-06-11 /pmc/articles/PMC8195602/ /pubmed/34114949 http://dx.doi.org/10.7554/eLife.66222 Text en © 2021, Li et al https://creativecommons.org/licenses/by/4.0/This article is distributed under the terms of the Creative Commons Attribution License (https://creativecommons.org/licenses/by/4.0/) , which permits unrestricted use and redistribution provided that the original author and source are credited.
spellingShingle Cancer Biology
Li, Jia
Qin, Xuan
Shi, Jie
Wang, Xiaoshuang
Li, Tong
Xu, Mengyao
Chen, Xiaosu
Zhao, Yujia
Han, Jiahao
Piao, Yongjun
Zhang, Wenwen
Qu, Pengpeng
Wang, Longlong
Xiang, Rong
Shi, Yi
A systematic CRISPR screen reveals an IL-20/IL20RA-mediated immune crosstalk to prevent the ovarian cancer metastasis
title A systematic CRISPR screen reveals an IL-20/IL20RA-mediated immune crosstalk to prevent the ovarian cancer metastasis
title_full A systematic CRISPR screen reveals an IL-20/IL20RA-mediated immune crosstalk to prevent the ovarian cancer metastasis
title_fullStr A systematic CRISPR screen reveals an IL-20/IL20RA-mediated immune crosstalk to prevent the ovarian cancer metastasis
title_full_unstemmed A systematic CRISPR screen reveals an IL-20/IL20RA-mediated immune crosstalk to prevent the ovarian cancer metastasis
title_short A systematic CRISPR screen reveals an IL-20/IL20RA-mediated immune crosstalk to prevent the ovarian cancer metastasis
title_sort systematic crispr screen reveals an il-20/il20ra-mediated immune crosstalk to prevent the ovarian cancer metastasis
topic Cancer Biology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8195602/
https://www.ncbi.nlm.nih.gov/pubmed/34114949
http://dx.doi.org/10.7554/eLife.66222
work_keys_str_mv AT lijia asystematiccrisprscreenrevealsanil20il20ramediatedimmunecrosstalktopreventtheovariancancermetastasis
AT qinxuan asystematiccrisprscreenrevealsanil20il20ramediatedimmunecrosstalktopreventtheovariancancermetastasis
AT shijie asystematiccrisprscreenrevealsanil20il20ramediatedimmunecrosstalktopreventtheovariancancermetastasis
AT wangxiaoshuang asystematiccrisprscreenrevealsanil20il20ramediatedimmunecrosstalktopreventtheovariancancermetastasis
AT litong asystematiccrisprscreenrevealsanil20il20ramediatedimmunecrosstalktopreventtheovariancancermetastasis
AT xumengyao asystematiccrisprscreenrevealsanil20il20ramediatedimmunecrosstalktopreventtheovariancancermetastasis
AT chenxiaosu asystematiccrisprscreenrevealsanil20il20ramediatedimmunecrosstalktopreventtheovariancancermetastasis
AT zhaoyujia asystematiccrisprscreenrevealsanil20il20ramediatedimmunecrosstalktopreventtheovariancancermetastasis
AT hanjiahao asystematiccrisprscreenrevealsanil20il20ramediatedimmunecrosstalktopreventtheovariancancermetastasis
AT piaoyongjun asystematiccrisprscreenrevealsanil20il20ramediatedimmunecrosstalktopreventtheovariancancermetastasis
AT zhangwenwen asystematiccrisprscreenrevealsanil20il20ramediatedimmunecrosstalktopreventtheovariancancermetastasis
AT qupengpeng asystematiccrisprscreenrevealsanil20il20ramediatedimmunecrosstalktopreventtheovariancancermetastasis
AT wanglonglong asystematiccrisprscreenrevealsanil20il20ramediatedimmunecrosstalktopreventtheovariancancermetastasis
AT xiangrong asystematiccrisprscreenrevealsanil20il20ramediatedimmunecrosstalktopreventtheovariancancermetastasis
AT shiyi asystematiccrisprscreenrevealsanil20il20ramediatedimmunecrosstalktopreventtheovariancancermetastasis
AT lijia systematiccrisprscreenrevealsanil20il20ramediatedimmunecrosstalktopreventtheovariancancermetastasis
AT qinxuan systematiccrisprscreenrevealsanil20il20ramediatedimmunecrosstalktopreventtheovariancancermetastasis
AT shijie systematiccrisprscreenrevealsanil20il20ramediatedimmunecrosstalktopreventtheovariancancermetastasis
AT wangxiaoshuang systematiccrisprscreenrevealsanil20il20ramediatedimmunecrosstalktopreventtheovariancancermetastasis
AT litong systematiccrisprscreenrevealsanil20il20ramediatedimmunecrosstalktopreventtheovariancancermetastasis
AT xumengyao systematiccrisprscreenrevealsanil20il20ramediatedimmunecrosstalktopreventtheovariancancermetastasis
AT chenxiaosu systematiccrisprscreenrevealsanil20il20ramediatedimmunecrosstalktopreventtheovariancancermetastasis
AT zhaoyujia systematiccrisprscreenrevealsanil20il20ramediatedimmunecrosstalktopreventtheovariancancermetastasis
AT hanjiahao systematiccrisprscreenrevealsanil20il20ramediatedimmunecrosstalktopreventtheovariancancermetastasis
AT piaoyongjun systematiccrisprscreenrevealsanil20il20ramediatedimmunecrosstalktopreventtheovariancancermetastasis
AT zhangwenwen systematiccrisprscreenrevealsanil20il20ramediatedimmunecrosstalktopreventtheovariancancermetastasis
AT qupengpeng systematiccrisprscreenrevealsanil20il20ramediatedimmunecrosstalktopreventtheovariancancermetastasis
AT wanglonglong systematiccrisprscreenrevealsanil20il20ramediatedimmunecrosstalktopreventtheovariancancermetastasis
AT xiangrong systematiccrisprscreenrevealsanil20il20ramediatedimmunecrosstalktopreventtheovariancancermetastasis
AT shiyi systematiccrisprscreenrevealsanil20il20ramediatedimmunecrosstalktopreventtheovariancancermetastasis