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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...
Autores principales: | , , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
eLife Sciences Publications, Ltd
2021
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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 |
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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 |
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