RAS status and neoadjuvant chemotherapy impact CD8+ cells and tumor HLA class I expression in liver metastatic colorectal cancer
Abstract Background T lymphocytes and HLA expression on tumor cell both influence prognostic of localized colorectal cancer, but their role following chemotherapy in patients with liver metastatic colorectal cancer (mCRC) was not addressed. Methods One hundred fourteen patients treated in curative i...
Ausführliche Beschreibung
Autor*in: |
Fanny Ledys [verfasserIn] Quentin Klopfenstein [verfasserIn] Caroline Truntzer [verfasserIn] Laurent Arnould [verfasserIn] Julie Vincent [verfasserIn] Leila Bengrine [verfasserIn] Romain Remark [verfasserIn] Romain Boidot [verfasserIn] Sylvain Ladoire [verfasserIn] Francois Ghiringhelli [verfasserIn] Valentin Derangere [verfasserIn] |
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E-Artikel |
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Sprache: |
Englisch |
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2018 |
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Übergeordnetes Werk: |
In: Journal for ImmunoTherapy of Cancer - BMJ Publishing Group, 2013, 6(2018), 1, Seite 14 |
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Übergeordnetes Werk: |
volume:6 ; year:2018 ; number:1 ; pages:14 |
Links: |
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DOI / URN: |
10.1186/s40425-018-0438-3 |
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Katalog-ID: |
DOAJ069950490 |
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520 | |a Abstract Background T lymphocytes and HLA expression on tumor cell both influence prognostic of localized colorectal cancer, but their role following chemotherapy in patients with liver metastatic colorectal cancer (mCRC) was not addressed. Methods One hundred fourteen patients treated in curative intend of liver mCRC were included in this retrospective study. Patients were either untreated or treated with neoadjuvant therapy containing an anti-EGFR, bevacizumab or oxaliplatin. Immune densities were quantified in the tumor core and in invasive margin of metastases, using Qupath software or a pathologist’s quantification. CD8, NKp46, Foxp3, CD163, HLA, PD-L1 were analyzed and were correlated with progression free survival (PFS) and overall survival (OS) using multivariable Cox proportional hazards models. Results In the whole cohort only a high CD8+ cells infiltrate, a high HLA-I expression and wild-type RAS/RAF status were associated with a better overall survival in both univariate and multivariate model. Moreover, CD8+ cells immune infiltrate at invasive margin combined to HLA expression in cancer cell could increase patient’s outcome prediction. RAS status but not immune cell infiltrate was associated with HLA expression on tumor cells. In comparison to untreated patients, neoadjuvant chemotherapy induced CD8+ cells recruitment and increased PD-L1 staining in immune infiltrates only for WT RAS patients. In this context, anti-EGFR and oxaliplatin based chemotherapy are the most powerful to induce CD8+ cells mobilization within the metastatic site. Conclusions While CD8 infiltrate and HLA expression appear to be prognostic for mCRC, CD8 and PD-L1 infiltrate are enhanced by neoadjuvant chemotherapy in mCRC under RAS status dependence. | ||
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653 | 0 | |a Neoplasms. Tumors. Oncology. Including cancer and carcinogens | |
700 | 0 | |a Quentin Klopfenstein |e verfasserin |4 aut | |
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700 | 0 | |a Valentin Derangere |e verfasserin |4 aut | |
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10.1186/s40425-018-0438-3 doi (DE-627)DOAJ069950490 (DE-599)DOAJf4b2d253e348427284501126f50ab4c2 DE-627 ger DE-627 rakwb eng RC254-282 Fanny Ledys verfasserin aut RAS status and neoadjuvant chemotherapy impact CD8+ cells and tumor HLA class I expression in liver metastatic colorectal cancer 2018 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier Abstract Background T lymphocytes and HLA expression on tumor cell both influence prognostic of localized colorectal cancer, but their role following chemotherapy in patients with liver metastatic colorectal cancer (mCRC) was not addressed. Methods One hundred fourteen patients treated in curative intend of liver mCRC were included in this retrospective study. Patients were either untreated or treated with neoadjuvant therapy containing an anti-EGFR, bevacizumab or oxaliplatin. Immune densities were quantified in the tumor core and in invasive margin of metastases, using Qupath software or a pathologist’s quantification. CD8, NKp46, Foxp3, CD163, HLA, PD-L1 were analyzed and were correlated with progression free survival (PFS) and overall survival (OS) using multivariable Cox proportional hazards models. Results In the whole cohort only a high CD8+ cells infiltrate, a high HLA-I expression and wild-type RAS/RAF status were associated with a better overall survival in both univariate and multivariate model. Moreover, CD8+ cells immune infiltrate at invasive margin combined to HLA expression in cancer cell could increase patient’s outcome prediction. RAS status but not immune cell infiltrate was associated with HLA expression on tumor cells. In comparison to untreated patients, neoadjuvant chemotherapy induced CD8+ cells recruitment and increased PD-L1 staining in immune infiltrates only for WT RAS patients. In this context, anti-EGFR and oxaliplatin based chemotherapy are the most powerful to induce CD8+ cells mobilization within the metastatic site. Conclusions While CD8 infiltrate and HLA expression appear to be prognostic for mCRC, CD8 and PD-L1 infiltrate are enhanced by neoadjuvant chemotherapy in mCRC under RAS status dependence. Colorectal cancer Liver metastases CD8 HLA Neoplasms. Tumors. Oncology. Including cancer and carcinogens Quentin Klopfenstein verfasserin aut Caroline Truntzer verfasserin aut Laurent Arnould verfasserin aut Julie Vincent verfasserin aut Leila Bengrine verfasserin aut Romain Remark verfasserin aut Romain Boidot verfasserin aut Sylvain Ladoire verfasserin aut Francois Ghiringhelli verfasserin aut Valentin Derangere verfasserin aut In Journal for ImmunoTherapy of Cancer BMJ Publishing Group, 2013 6(2018), 1, Seite 14 (DE-627)750086335 (DE-600)2719863-7 20511426 nnns volume:6 year:2018 number:1 pages:14 https://doi.org/10.1186/s40425-018-0438-3 kostenfrei https://doaj.org/article/f4b2d253e348427284501126f50ab4c2 kostenfrei http://link.springer.com/article/10.1186/s40425-018-0438-3 kostenfrei https://doaj.org/toc/2051-1426 Journal toc kostenfrei GBV_USEFLAG_A SYSFLAG_A GBV_DOAJ SSG-OLC-PHA GBV_ILN_11 GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_31 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_73 GBV_ILN_74 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_206 GBV_ILN_213 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_2003 GBV_ILN_2014 GBV_ILN_4012 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4249 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4700 AR 6 2018 1 14 |
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10.1186/s40425-018-0438-3 doi (DE-627)DOAJ069950490 (DE-599)DOAJf4b2d253e348427284501126f50ab4c2 DE-627 ger DE-627 rakwb eng RC254-282 Fanny Ledys verfasserin aut RAS status and neoadjuvant chemotherapy impact CD8+ cells and tumor HLA class I expression in liver metastatic colorectal cancer 2018 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier Abstract Background T lymphocytes and HLA expression on tumor cell both influence prognostic of localized colorectal cancer, but their role following chemotherapy in patients with liver metastatic colorectal cancer (mCRC) was not addressed. Methods One hundred fourteen patients treated in curative intend of liver mCRC were included in this retrospective study. Patients were either untreated or treated with neoadjuvant therapy containing an anti-EGFR, bevacizumab or oxaliplatin. Immune densities were quantified in the tumor core and in invasive margin of metastases, using Qupath software or a pathologist’s quantification. CD8, NKp46, Foxp3, CD163, HLA, PD-L1 were analyzed and were correlated with progression free survival (PFS) and overall survival (OS) using multivariable Cox proportional hazards models. Results In the whole cohort only a high CD8+ cells infiltrate, a high HLA-I expression and wild-type RAS/RAF status were associated with a better overall survival in both univariate and multivariate model. Moreover, CD8+ cells immune infiltrate at invasive margin combined to HLA expression in cancer cell could increase patient’s outcome prediction. RAS status but not immune cell infiltrate was associated with HLA expression on tumor cells. In comparison to untreated patients, neoadjuvant chemotherapy induced CD8+ cells recruitment and increased PD-L1 staining in immune infiltrates only for WT RAS patients. In this context, anti-EGFR and oxaliplatin based chemotherapy are the most powerful to induce CD8+ cells mobilization within the metastatic site. Conclusions While CD8 infiltrate and HLA expression appear to be prognostic for mCRC, CD8 and PD-L1 infiltrate are enhanced by neoadjuvant chemotherapy in mCRC under RAS status dependence. Colorectal cancer Liver metastases CD8 HLA Neoplasms. Tumors. Oncology. Including cancer and carcinogens Quentin Klopfenstein verfasserin aut Caroline Truntzer verfasserin aut Laurent Arnould verfasserin aut Julie Vincent verfasserin aut Leila Bengrine verfasserin aut Romain Remark verfasserin aut Romain Boidot verfasserin aut Sylvain Ladoire verfasserin aut Francois Ghiringhelli verfasserin aut Valentin Derangere verfasserin aut In Journal for ImmunoTherapy of Cancer BMJ Publishing Group, 2013 6(2018), 1, Seite 14 (DE-627)750086335 (DE-600)2719863-7 20511426 nnns volume:6 year:2018 number:1 pages:14 https://doi.org/10.1186/s40425-018-0438-3 kostenfrei https://doaj.org/article/f4b2d253e348427284501126f50ab4c2 kostenfrei http://link.springer.com/article/10.1186/s40425-018-0438-3 kostenfrei https://doaj.org/toc/2051-1426 Journal toc kostenfrei GBV_USEFLAG_A SYSFLAG_A GBV_DOAJ SSG-OLC-PHA GBV_ILN_11 GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_31 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_73 GBV_ILN_74 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_206 GBV_ILN_213 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_2003 GBV_ILN_2014 GBV_ILN_4012 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4249 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4700 AR 6 2018 1 14 |
allfields_unstemmed |
10.1186/s40425-018-0438-3 doi (DE-627)DOAJ069950490 (DE-599)DOAJf4b2d253e348427284501126f50ab4c2 DE-627 ger DE-627 rakwb eng RC254-282 Fanny Ledys verfasserin aut RAS status and neoadjuvant chemotherapy impact CD8+ cells and tumor HLA class I expression in liver metastatic colorectal cancer 2018 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier Abstract Background T lymphocytes and HLA expression on tumor cell both influence prognostic of localized colorectal cancer, but their role following chemotherapy in patients with liver metastatic colorectal cancer (mCRC) was not addressed. Methods One hundred fourteen patients treated in curative intend of liver mCRC were included in this retrospective study. Patients were either untreated or treated with neoadjuvant therapy containing an anti-EGFR, bevacizumab or oxaliplatin. Immune densities were quantified in the tumor core and in invasive margin of metastases, using Qupath software or a pathologist’s quantification. CD8, NKp46, Foxp3, CD163, HLA, PD-L1 were analyzed and were correlated with progression free survival (PFS) and overall survival (OS) using multivariable Cox proportional hazards models. Results In the whole cohort only a high CD8+ cells infiltrate, a high HLA-I expression and wild-type RAS/RAF status were associated with a better overall survival in both univariate and multivariate model. Moreover, CD8+ cells immune infiltrate at invasive margin combined to HLA expression in cancer cell could increase patient’s outcome prediction. RAS status but not immune cell infiltrate was associated with HLA expression on tumor cells. In comparison to untreated patients, neoadjuvant chemotherapy induced CD8+ cells recruitment and increased PD-L1 staining in immune infiltrates only for WT RAS patients. In this context, anti-EGFR and oxaliplatin based chemotherapy are the most powerful to induce CD8+ cells mobilization within the metastatic site. Conclusions While CD8 infiltrate and HLA expression appear to be prognostic for mCRC, CD8 and PD-L1 infiltrate are enhanced by neoadjuvant chemotherapy in mCRC under RAS status dependence. Colorectal cancer Liver metastases CD8 HLA Neoplasms. Tumors. Oncology. Including cancer and carcinogens Quentin Klopfenstein verfasserin aut Caroline Truntzer verfasserin aut Laurent Arnould verfasserin aut Julie Vincent verfasserin aut Leila Bengrine verfasserin aut Romain Remark verfasserin aut Romain Boidot verfasserin aut Sylvain Ladoire verfasserin aut Francois Ghiringhelli verfasserin aut Valentin Derangere verfasserin aut In Journal for ImmunoTherapy of Cancer BMJ Publishing Group, 2013 6(2018), 1, Seite 14 (DE-627)750086335 (DE-600)2719863-7 20511426 nnns volume:6 year:2018 number:1 pages:14 https://doi.org/10.1186/s40425-018-0438-3 kostenfrei https://doaj.org/article/f4b2d253e348427284501126f50ab4c2 kostenfrei http://link.springer.com/article/10.1186/s40425-018-0438-3 kostenfrei https://doaj.org/toc/2051-1426 Journal toc kostenfrei GBV_USEFLAG_A SYSFLAG_A GBV_DOAJ SSG-OLC-PHA GBV_ILN_11 GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_31 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_73 GBV_ILN_74 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_206 GBV_ILN_213 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_2003 GBV_ILN_2014 GBV_ILN_4012 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4249 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4700 AR 6 2018 1 14 |
allfieldsGer |
10.1186/s40425-018-0438-3 doi (DE-627)DOAJ069950490 (DE-599)DOAJf4b2d253e348427284501126f50ab4c2 DE-627 ger DE-627 rakwb eng RC254-282 Fanny Ledys verfasserin aut RAS status and neoadjuvant chemotherapy impact CD8+ cells and tumor HLA class I expression in liver metastatic colorectal cancer 2018 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier Abstract Background T lymphocytes and HLA expression on tumor cell both influence prognostic of localized colorectal cancer, but their role following chemotherapy in patients with liver metastatic colorectal cancer (mCRC) was not addressed. Methods One hundred fourteen patients treated in curative intend of liver mCRC were included in this retrospective study. Patients were either untreated or treated with neoadjuvant therapy containing an anti-EGFR, bevacizumab or oxaliplatin. Immune densities were quantified in the tumor core and in invasive margin of metastases, using Qupath software or a pathologist’s quantification. CD8, NKp46, Foxp3, CD163, HLA, PD-L1 were analyzed and were correlated with progression free survival (PFS) and overall survival (OS) using multivariable Cox proportional hazards models. Results In the whole cohort only a high CD8+ cells infiltrate, a high HLA-I expression and wild-type RAS/RAF status were associated with a better overall survival in both univariate and multivariate model. Moreover, CD8+ cells immune infiltrate at invasive margin combined to HLA expression in cancer cell could increase patient’s outcome prediction. RAS status but not immune cell infiltrate was associated with HLA expression on tumor cells. In comparison to untreated patients, neoadjuvant chemotherapy induced CD8+ cells recruitment and increased PD-L1 staining in immune infiltrates only for WT RAS patients. In this context, anti-EGFR and oxaliplatin based chemotherapy are the most powerful to induce CD8+ cells mobilization within the metastatic site. Conclusions While CD8 infiltrate and HLA expression appear to be prognostic for mCRC, CD8 and PD-L1 infiltrate are enhanced by neoadjuvant chemotherapy in mCRC under RAS status dependence. Colorectal cancer Liver metastases CD8 HLA Neoplasms. Tumors. Oncology. Including cancer and carcinogens Quentin Klopfenstein verfasserin aut Caroline Truntzer verfasserin aut Laurent Arnould verfasserin aut Julie Vincent verfasserin aut Leila Bengrine verfasserin aut Romain Remark verfasserin aut Romain Boidot verfasserin aut Sylvain Ladoire verfasserin aut Francois Ghiringhelli verfasserin aut Valentin Derangere verfasserin aut In Journal for ImmunoTherapy of Cancer BMJ Publishing Group, 2013 6(2018), 1, Seite 14 (DE-627)750086335 (DE-600)2719863-7 20511426 nnns volume:6 year:2018 number:1 pages:14 https://doi.org/10.1186/s40425-018-0438-3 kostenfrei https://doaj.org/article/f4b2d253e348427284501126f50ab4c2 kostenfrei http://link.springer.com/article/10.1186/s40425-018-0438-3 kostenfrei https://doaj.org/toc/2051-1426 Journal toc kostenfrei GBV_USEFLAG_A SYSFLAG_A GBV_DOAJ SSG-OLC-PHA GBV_ILN_11 GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_31 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_73 GBV_ILN_74 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_206 GBV_ILN_213 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_2003 GBV_ILN_2014 GBV_ILN_4012 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4249 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4700 AR 6 2018 1 14 |
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10.1186/s40425-018-0438-3 doi (DE-627)DOAJ069950490 (DE-599)DOAJf4b2d253e348427284501126f50ab4c2 DE-627 ger DE-627 rakwb eng RC254-282 Fanny Ledys verfasserin aut RAS status and neoadjuvant chemotherapy impact CD8+ cells and tumor HLA class I expression in liver metastatic colorectal cancer 2018 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier Abstract Background T lymphocytes and HLA expression on tumor cell both influence prognostic of localized colorectal cancer, but their role following chemotherapy in patients with liver metastatic colorectal cancer (mCRC) was not addressed. Methods One hundred fourteen patients treated in curative intend of liver mCRC were included in this retrospective study. Patients were either untreated or treated with neoadjuvant therapy containing an anti-EGFR, bevacizumab or oxaliplatin. Immune densities were quantified in the tumor core and in invasive margin of metastases, using Qupath software or a pathologist’s quantification. CD8, NKp46, Foxp3, CD163, HLA, PD-L1 were analyzed and were correlated with progression free survival (PFS) and overall survival (OS) using multivariable Cox proportional hazards models. Results In the whole cohort only a high CD8+ cells infiltrate, a high HLA-I expression and wild-type RAS/RAF status were associated with a better overall survival in both univariate and multivariate model. Moreover, CD8+ cells immune infiltrate at invasive margin combined to HLA expression in cancer cell could increase patient’s outcome prediction. RAS status but not immune cell infiltrate was associated with HLA expression on tumor cells. In comparison to untreated patients, neoadjuvant chemotherapy induced CD8+ cells recruitment and increased PD-L1 staining in immune infiltrates only for WT RAS patients. In this context, anti-EGFR and oxaliplatin based chemotherapy are the most powerful to induce CD8+ cells mobilization within the metastatic site. Conclusions While CD8 infiltrate and HLA expression appear to be prognostic for mCRC, CD8 and PD-L1 infiltrate are enhanced by neoadjuvant chemotherapy in mCRC under RAS status dependence. Colorectal cancer Liver metastases CD8 HLA Neoplasms. Tumors. Oncology. Including cancer and carcinogens Quentin Klopfenstein verfasserin aut Caroline Truntzer verfasserin aut Laurent Arnould verfasserin aut Julie Vincent verfasserin aut Leila Bengrine verfasserin aut Romain Remark verfasserin aut Romain Boidot verfasserin aut Sylvain Ladoire verfasserin aut Francois Ghiringhelli verfasserin aut Valentin Derangere verfasserin aut In Journal for ImmunoTherapy of Cancer BMJ Publishing Group, 2013 6(2018), 1, Seite 14 (DE-627)750086335 (DE-600)2719863-7 20511426 nnns volume:6 year:2018 number:1 pages:14 https://doi.org/10.1186/s40425-018-0438-3 kostenfrei https://doaj.org/article/f4b2d253e348427284501126f50ab4c2 kostenfrei http://link.springer.com/article/10.1186/s40425-018-0438-3 kostenfrei https://doaj.org/toc/2051-1426 Journal toc kostenfrei GBV_USEFLAG_A SYSFLAG_A GBV_DOAJ SSG-OLC-PHA GBV_ILN_11 GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_31 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_73 GBV_ILN_74 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_206 GBV_ILN_213 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_2003 GBV_ILN_2014 GBV_ILN_4012 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4249 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4700 AR 6 2018 1 14 |
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RAS status and neoadjuvant chemotherapy impact CD8+ cells and tumor HLA class I expression in liver metastatic colorectal cancer |
abstract |
Abstract Background T lymphocytes and HLA expression on tumor cell both influence prognostic of localized colorectal cancer, but their role following chemotherapy in patients with liver metastatic colorectal cancer (mCRC) was not addressed. Methods One hundred fourteen patients treated in curative intend of liver mCRC were included in this retrospective study. Patients were either untreated or treated with neoadjuvant therapy containing an anti-EGFR, bevacizumab or oxaliplatin. Immune densities were quantified in the tumor core and in invasive margin of metastases, using Qupath software or a pathologist’s quantification. CD8, NKp46, Foxp3, CD163, HLA, PD-L1 were analyzed and were correlated with progression free survival (PFS) and overall survival (OS) using multivariable Cox proportional hazards models. Results In the whole cohort only a high CD8+ cells infiltrate, a high HLA-I expression and wild-type RAS/RAF status were associated with a better overall survival in both univariate and multivariate model. Moreover, CD8+ cells immune infiltrate at invasive margin combined to HLA expression in cancer cell could increase patient’s outcome prediction. RAS status but not immune cell infiltrate was associated with HLA expression on tumor cells. In comparison to untreated patients, neoadjuvant chemotherapy induced CD8+ cells recruitment and increased PD-L1 staining in immune infiltrates only for WT RAS patients. In this context, anti-EGFR and oxaliplatin based chemotherapy are the most powerful to induce CD8+ cells mobilization within the metastatic site. Conclusions While CD8 infiltrate and HLA expression appear to be prognostic for mCRC, CD8 and PD-L1 infiltrate are enhanced by neoadjuvant chemotherapy in mCRC under RAS status dependence. |
abstractGer |
Abstract Background T lymphocytes and HLA expression on tumor cell both influence prognostic of localized colorectal cancer, but their role following chemotherapy in patients with liver metastatic colorectal cancer (mCRC) was not addressed. Methods One hundred fourteen patients treated in curative intend of liver mCRC were included in this retrospective study. Patients were either untreated or treated with neoadjuvant therapy containing an anti-EGFR, bevacizumab or oxaliplatin. Immune densities were quantified in the tumor core and in invasive margin of metastases, using Qupath software or a pathologist’s quantification. CD8, NKp46, Foxp3, CD163, HLA, PD-L1 were analyzed and were correlated with progression free survival (PFS) and overall survival (OS) using multivariable Cox proportional hazards models. Results In the whole cohort only a high CD8+ cells infiltrate, a high HLA-I expression and wild-type RAS/RAF status were associated with a better overall survival in both univariate and multivariate model. Moreover, CD8+ cells immune infiltrate at invasive margin combined to HLA expression in cancer cell could increase patient’s outcome prediction. RAS status but not immune cell infiltrate was associated with HLA expression on tumor cells. In comparison to untreated patients, neoadjuvant chemotherapy induced CD8+ cells recruitment and increased PD-L1 staining in immune infiltrates only for WT RAS patients. In this context, anti-EGFR and oxaliplatin based chemotherapy are the most powerful to induce CD8+ cells mobilization within the metastatic site. Conclusions While CD8 infiltrate and HLA expression appear to be prognostic for mCRC, CD8 and PD-L1 infiltrate are enhanced by neoadjuvant chemotherapy in mCRC under RAS status dependence. |
abstract_unstemmed |
Abstract Background T lymphocytes and HLA expression on tumor cell both influence prognostic of localized colorectal cancer, but their role following chemotherapy in patients with liver metastatic colorectal cancer (mCRC) was not addressed. Methods One hundred fourteen patients treated in curative intend of liver mCRC were included in this retrospective study. Patients were either untreated or treated with neoadjuvant therapy containing an anti-EGFR, bevacizumab or oxaliplatin. Immune densities were quantified in the tumor core and in invasive margin of metastases, using Qupath software or a pathologist’s quantification. CD8, NKp46, Foxp3, CD163, HLA, PD-L1 were analyzed and were correlated with progression free survival (PFS) and overall survival (OS) using multivariable Cox proportional hazards models. Results In the whole cohort only a high CD8+ cells infiltrate, a high HLA-I expression and wild-type RAS/RAF status were associated with a better overall survival in both univariate and multivariate model. Moreover, CD8+ cells immune infiltrate at invasive margin combined to HLA expression in cancer cell could increase patient’s outcome prediction. RAS status but not immune cell infiltrate was associated with HLA expression on tumor cells. In comparison to untreated patients, neoadjuvant chemotherapy induced CD8+ cells recruitment and increased PD-L1 staining in immune infiltrates only for WT RAS patients. In this context, anti-EGFR and oxaliplatin based chemotherapy are the most powerful to induce CD8+ cells mobilization within the metastatic site. Conclusions While CD8 infiltrate and HLA expression appear to be prognostic for mCRC, CD8 and PD-L1 infiltrate are enhanced by neoadjuvant chemotherapy in mCRC under RAS status dependence. |
collection_details |
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container_issue |
1 |
title_short |
RAS status and neoadjuvant chemotherapy impact CD8+ cells and tumor HLA class I expression in liver metastatic colorectal cancer |
url |
https://doi.org/10.1186/s40425-018-0438-3 https://doaj.org/article/f4b2d253e348427284501126f50ab4c2 http://link.springer.com/article/10.1186/s40425-018-0438-3 https://doaj.org/toc/2051-1426 |
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author2 |
Quentin Klopfenstein Caroline Truntzer Laurent Arnould Julie Vincent Leila Bengrine Romain Remark Romain Boidot Sylvain Ladoire Francois Ghiringhelli Valentin Derangere |
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Quentin Klopfenstein Caroline Truntzer Laurent Arnould Julie Vincent Leila Bengrine Romain Remark Romain Boidot Sylvain Ladoire Francois Ghiringhelli Valentin Derangere |
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up_date |
2024-07-04T01:16:05.200Z |
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