SLFN11 captures cancer-immunity interactions associated with platinum sensitivity in high-grade serous ovarian cancer
<p dir="ltr">Large independent analyses on cancer cell lines followed by functional studies have identified Schlafen 11 (SLFN11), a putative helicase, as the strongest predictor of sensitivity to DNA-damaging agents (DDAs), including platinum. However, its role as a prognostic biomar...
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2021
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| _version_ | 1864513515274895360 |
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| author | Claudia Winkler (436853) |
| author2 | Matthew King (782718) Julie Berthe (18595747) Domenico Ferraioli (15006216) Anna Garuti (212195) Federica Grillo (5306969) Jaime Rodriguez-Canales (436827) Lorenzo Ferrando (6648539) Nicolas Chopin (6114131) Isabelle Ray-Coquard (346757) Oona Delpuech (423602) Davide Bedognetti (2632474) Alberto Ballestrero (212236) Elisabetta Leo (16336) Gabriele Zoppoli (201733) |
| author2_role | author author author author author author author author author author author author author author |
| author_facet | Claudia Winkler (436853) Matthew King (782718) Julie Berthe (18595747) Domenico Ferraioli (15006216) Anna Garuti (212195) Federica Grillo (5306969) Jaime Rodriguez-Canales (436827) Lorenzo Ferrando (6648539) Nicolas Chopin (6114131) Isabelle Ray-Coquard (346757) Oona Delpuech (423602) Davide Bedognetti (2632474) Alberto Ballestrero (212236) Elisabetta Leo (16336) Gabriele Zoppoli (201733) |
| author_role | author |
| dc.creator.none.fl_str_mv | Claudia Winkler (436853) Matthew King (782718) Julie Berthe (18595747) Domenico Ferraioli (15006216) Anna Garuti (212195) Federica Grillo (5306969) Jaime Rodriguez-Canales (436827) Lorenzo Ferrando (6648539) Nicolas Chopin (6114131) Isabelle Ray-Coquard (346757) Oona Delpuech (423602) Davide Bedognetti (2632474) Alberto Ballestrero (212236) Elisabetta Leo (16336) Gabriele Zoppoli (201733) |
| dc.date.none.fl_str_mv | 2021-09-22T03:00:00Z |
| dc.identifier.none.fl_str_mv | 10.1172/jci.insight.146098 |
| dc.relation.none.fl_str_mv | https://figshare.com/articles/journal_contribution/SLFN11_captures_cancer-immunity_interactions_associated_with_platinum_sensitivity_in_high-grade_serous_ovarian_cancer/25878232 |
| dc.rights.none.fl_str_mv | CC BY 4.0 info:eu-repo/semantics/openAccess |
| dc.subject.none.fl_str_mv | Biomedical and clinical sciences Immunology Oncology and carcinogenesis Platinum-based chemotherapy Prognostic biomarker Human cancer samples High-grade serous ovarian carcinoma (HGSOC) Neoplastic components Microenvironment |
| dc.title.none.fl_str_mv | SLFN11 captures cancer-immunity interactions associated with platinum sensitivity in high-grade serous ovarian cancer |
| dc.type.none.fl_str_mv | Text Journal contribution info:eu-repo/semantics/publishedVersion text contribution to journal |
| description | <p dir="ltr">Large independent analyses on cancer cell lines followed by functional studies have identified Schlafen 11 (SLFN11), a putative helicase, as the strongest predictor of sensitivity to DNA-damaging agents (DDAs), including platinum. However, its role as a prognostic biomarker is undefined, partially due to the lack of validated methods to score SLFN11 in human tissues. Here, we implemented a pipeline to quantify SLFN11 in human cancer samples. By analyzing a cohort of high-grade serous ovarian carcinoma (HGSOC) specimens before platinum-based chemotherapy treatment, we show, for the first time to our knowledge, that SLFN11 density in both the neoplastic and microenvironmental components was independently associated with favorable outcome. We observed SLFN11 expression in both infiltrating innate and adaptive immune cells, and analyses in a second, independent, cohort revealed that SLFN11 was associated with immune activation in HGSOC. We found that platinum treatments activated immune-related pathways in ovarian cancer cells in an SLFN11-dependent manner, representative of tumor-immune transactivation. Moreover, SLFN11 expression was induced in activated, isolated immune cell subpopulations, hinting that SLFN11 in the immune compartment may be an indicator of immune transactivation. In summary, we propose SLFN11 is a dual biomarker capturing simultaneously interconnected immunological and cancer cell–intrinsic functional dispositions associated with sensitivity to DDA treatment.</p><h2>Other Information</h2><p dir="ltr">Published in: JCI Insight<br>License: <a href="http://creativecommons.org/licenses/by/4.0/" target="_blank">http://creativecommons.org/licenses/by/4.0/</a><br>See article on publisher's website: <a href="https://dx.doi.org/10.1172/jci.insight.146098" target="_blank">https://dx.doi.org/10.1172/jci.insight.146098</a></p> |
| eu_rights_str_mv | openAccess |
| id | Manara2_01a0718d8ebac4c6e836c9145f426c3d |
| identifier_str_mv | 10.1172/jci.insight.146098 |
| network_acronym_str | Manara2 |
| network_name_str | Manara2 |
| oai_identifier_str | oai:figshare.com:article/25878232 |
| publishDate | 2021 |
| repository.mail.fl_str_mv | |
| repository.name.fl_str_mv | |
| repository_id_str | |
| rights_invalid_str_mv | CC BY 4.0 |
| spelling | SLFN11 captures cancer-immunity interactions associated with platinum sensitivity in high-grade serous ovarian cancerClaudia Winkler (436853)Matthew King (782718)Julie Berthe (18595747)Domenico Ferraioli (15006216)Anna Garuti (212195)Federica Grillo (5306969)Jaime Rodriguez-Canales (436827)Lorenzo Ferrando (6648539)Nicolas Chopin (6114131)Isabelle Ray-Coquard (346757)Oona Delpuech (423602)Davide Bedognetti (2632474)Alberto Ballestrero (212236)Elisabetta Leo (16336)Gabriele Zoppoli (201733)Biomedical and clinical sciencesImmunologyOncology and carcinogenesisPlatinum-based chemotherapyPrognostic biomarkerHuman cancer samplesHigh-grade serous ovarian carcinoma (HGSOC)Neoplastic componentsMicroenvironment<p dir="ltr">Large independent analyses on cancer cell lines followed by functional studies have identified Schlafen 11 (SLFN11), a putative helicase, as the strongest predictor of sensitivity to DNA-damaging agents (DDAs), including platinum. However, its role as a prognostic biomarker is undefined, partially due to the lack of validated methods to score SLFN11 in human tissues. Here, we implemented a pipeline to quantify SLFN11 in human cancer samples. By analyzing a cohort of high-grade serous ovarian carcinoma (HGSOC) specimens before platinum-based chemotherapy treatment, we show, for the first time to our knowledge, that SLFN11 density in both the neoplastic and microenvironmental components was independently associated with favorable outcome. We observed SLFN11 expression in both infiltrating innate and adaptive immune cells, and analyses in a second, independent, cohort revealed that SLFN11 was associated with immune activation in HGSOC. We found that platinum treatments activated immune-related pathways in ovarian cancer cells in an SLFN11-dependent manner, representative of tumor-immune transactivation. Moreover, SLFN11 expression was induced in activated, isolated immune cell subpopulations, hinting that SLFN11 in the immune compartment may be an indicator of immune transactivation. In summary, we propose SLFN11 is a dual biomarker capturing simultaneously interconnected immunological and cancer cell–intrinsic functional dispositions associated with sensitivity to DDA treatment.</p><h2>Other Information</h2><p dir="ltr">Published in: JCI Insight<br>License: <a href="http://creativecommons.org/licenses/by/4.0/" target="_blank">http://creativecommons.org/licenses/by/4.0/</a><br>See article on publisher's website: <a href="https://dx.doi.org/10.1172/jci.insight.146098" target="_blank">https://dx.doi.org/10.1172/jci.insight.146098</a></p>2021-09-22T03:00:00ZTextJournal contributioninfo:eu-repo/semantics/publishedVersiontextcontribution to journal10.1172/jci.insight.146098https://figshare.com/articles/journal_contribution/SLFN11_captures_cancer-immunity_interactions_associated_with_platinum_sensitivity_in_high-grade_serous_ovarian_cancer/25878232CC BY 4.0info:eu-repo/semantics/openAccessoai:figshare.com:article/258782322021-09-22T03:00:00Z |
| spellingShingle | SLFN11 captures cancer-immunity interactions associated with platinum sensitivity in high-grade serous ovarian cancer Claudia Winkler (436853) Biomedical and clinical sciences Immunology Oncology and carcinogenesis Platinum-based chemotherapy Prognostic biomarker Human cancer samples High-grade serous ovarian carcinoma (HGSOC) Neoplastic components Microenvironment |
| status_str | publishedVersion |
| title | SLFN11 captures cancer-immunity interactions associated with platinum sensitivity in high-grade serous ovarian cancer |
| title_full | SLFN11 captures cancer-immunity interactions associated with platinum sensitivity in high-grade serous ovarian cancer |
| title_fullStr | SLFN11 captures cancer-immunity interactions associated with platinum sensitivity in high-grade serous ovarian cancer |
| title_full_unstemmed | SLFN11 captures cancer-immunity interactions associated with platinum sensitivity in high-grade serous ovarian cancer |
| title_short | SLFN11 captures cancer-immunity interactions associated with platinum sensitivity in high-grade serous ovarian cancer |
| title_sort | SLFN11 captures cancer-immunity interactions associated with platinum sensitivity in high-grade serous ovarian cancer |
| topic | Biomedical and clinical sciences Immunology Oncology and carcinogenesis Platinum-based chemotherapy Prognostic biomarker Human cancer samples High-grade serous ovarian carcinoma (HGSOC) Neoplastic components Microenvironment |