Circulating CD14high CD16low intermediate blood monocytes as a biomarker of ascites immune status and ovarian cancer progression
Background Besides the interest of an early detection of ovarian cancer, there is an urgent need for new predictive and prognostic biomarkers of tumor development and cancer treatment. In healthy patients, circulating blood monocytes are typically subdivided into classical (85%), intermediate (5%) a...
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doaj-0b2540fb3f554340aaa02a1869f2470b2021-07-19T12:02:00ZengBMJ Publishing GroupJournal for ImmunoTherapy of Cancer2051-14262020-06-018110.1136/jitc-2019-000472Circulating CD14high CD16low intermediate blood monocytes as a biomarker of ascites immune status and ovarian cancer progressionMélissa Prat0Augustin Le Naour1Kimberley Coulson2Fanny Lemée3Godefroy Jacquemin4Mouna Chirine Rahabi5Léa Lemaitre6Jean-Marc Barret7Maha Ayyoub8Jean-Pierre Delord9Isabelle Tabah-Fisch10Jean-François Prost11Bettina Couderc121 UMR152 Pharmadev, Université Toulouse III Paul Sabatier, Toulouse, Occitanie, France 1 UMR152 Pharmadev, Université Toulouse III Paul Sabatier, Toulouse, Occitanie, France 1 UMR152 Pharmadev, Université Toulouse III Paul Sabatier, Toulouse, Occitanie, France 5 Gamamabs Pharma, Toulouse, Languedoc-Roussillon-Midi, France1 UMR152 Pharmadev, Université Toulouse III Paul Sabatier, Toulouse, Occitanie, France 1 UMR152 Pharmadev, Université Toulouse III Paul Sabatier, Toulouse, Occitanie, France 3 UMR1037, CRCT, Toulouse, Midi-Pyrénées, France 5 Gamamabs Pharma, Toulouse, Languedoc-Roussillon-Midi, France3 UMR1037, CRCT, Toulouse, Midi-Pyrénées, France4 Institut Claudius Regaud, IUCT Oncopole, Toulouse, Languedoc-Roussillon-Midi, France 5 Gamamabs Pharma, Toulouse, Languedoc-Roussillon-Midi, France5 Gamamabs Pharma, Toulouse, Languedoc-Roussillon-Midi, France3 UMR1037, CRCT, Toulouse, Midi-Pyrénées, France Background Besides the interest of an early detection of ovarian cancer, there is an urgent need for new predictive and prognostic biomarkers of tumor development and cancer treatment. In healthy patients, circulating blood monocytes are typically subdivided into classical (85%), intermediate (5%) and non-classical (10%) populations. Although these circulating monocyte subsets have been suggested as biomarkers in several diseases, few studies have investigate their potential as a predictive signature for tumor immune status,tumor growth and treatment adaptation.Methods In this study, we used a homogeneous cohort of 28 chemotherapy-naïve patients with ovarian cancer to evaluate monocyte subsets as biomarkers of the ascites immunological status. We evaluated the correlations between circulating monocyte subsets and immune cells and tumor burden in peritoneal ascites. Moreover, to validate the use of circulating monocyte subsets tofollow tumor progression and treatment response, we characterized blood monocytes from ovarian cancer patients included in a phase 1 clinical trial at baseline and following murlentamab treatment.Results We demonstrate here a robust expansion of the intermediate blood monocytes (IBMs) in ovarian cancer patients. We establish a significant positive correlation between IBM percentage and tumor–associate macrophages with a CCR2high/CD163high/CD206high/CD86lowprofile. Moreover, IBM expansion is associated with a decreased effector/regulatory T-cell ratio in ascites and with the presence of soluble immunosuppressive mediators. We also establish that IBM proportion positively correlates with the peritoneum tumor burden. Finally, the study of IBMs in patients with ovarian cancer under immunotherapy during the phase clinical trial supports IBMs to follow the evolution of tumor development and the treatment adaptation.Conclusions This study, which links IBM level with immunosuppression and tumor burden in peritoneum, identifies IBMs as apotential predictive signature of ascites immune status and as a biomarker ofovarian cancer development and treatment response.Trial registration number EudraCT: 2015-004252-22 NCT02978755.https://jitc.bmj.com/content/8/1/e000472.full |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Mélissa Prat Augustin Le Naour Kimberley Coulson Fanny Lemée Godefroy Jacquemin Mouna Chirine Rahabi Léa Lemaitre Jean-Marc Barret Maha Ayyoub Jean-Pierre Delord Isabelle Tabah-Fisch Jean-François Prost Bettina Couderc |
spellingShingle |
Mélissa Prat Augustin Le Naour Kimberley Coulson Fanny Lemée Godefroy Jacquemin Mouna Chirine Rahabi Léa Lemaitre Jean-Marc Barret Maha Ayyoub Jean-Pierre Delord Isabelle Tabah-Fisch Jean-François Prost Bettina Couderc Circulating CD14high CD16low intermediate blood monocytes as a biomarker of ascites immune status and ovarian cancer progression Journal for ImmunoTherapy of Cancer |
author_facet |
Mélissa Prat Augustin Le Naour Kimberley Coulson Fanny Lemée Godefroy Jacquemin Mouna Chirine Rahabi Léa Lemaitre Jean-Marc Barret Maha Ayyoub Jean-Pierre Delord Isabelle Tabah-Fisch Jean-François Prost Bettina Couderc |
author_sort |
Mélissa Prat |
title |
Circulating CD14high CD16low intermediate blood monocytes as a biomarker of ascites immune status and ovarian cancer progression |
title_short |
Circulating CD14high CD16low intermediate blood monocytes as a biomarker of ascites immune status and ovarian cancer progression |
title_full |
Circulating CD14high CD16low intermediate blood monocytes as a biomarker of ascites immune status and ovarian cancer progression |
title_fullStr |
Circulating CD14high CD16low intermediate blood monocytes as a biomarker of ascites immune status and ovarian cancer progression |
title_full_unstemmed |
Circulating CD14high CD16low intermediate blood monocytes as a biomarker of ascites immune status and ovarian cancer progression |
title_sort |
circulating cd14high cd16low intermediate blood monocytes as a biomarker of ascites immune status and ovarian cancer progression |
publisher |
BMJ Publishing Group |
series |
Journal for ImmunoTherapy of Cancer |
issn |
2051-1426 |
publishDate |
2020-06-01 |
description |
Background Besides the interest of an early detection of ovarian cancer, there is an urgent need for new predictive and prognostic biomarkers of tumor development and cancer treatment. In healthy patients, circulating blood monocytes are typically subdivided into classical (85%), intermediate (5%) and non-classical (10%) populations. Although these circulating monocyte subsets have been suggested as biomarkers in several diseases, few studies have investigate their potential as a predictive signature for tumor immune status,tumor growth and treatment adaptation.Methods In this study, we used a homogeneous cohort of 28 chemotherapy-naïve patients with ovarian cancer to evaluate monocyte subsets as biomarkers of the ascites immunological status. We evaluated the correlations between circulating monocyte subsets and immune cells and tumor burden in peritoneal ascites. Moreover, to validate the use of circulating monocyte subsets tofollow tumor progression and treatment response, we characterized blood monocytes from ovarian cancer patients included in a phase 1 clinical trial at baseline and following murlentamab treatment.Results We demonstrate here a robust expansion of the intermediate blood monocytes (IBMs) in ovarian cancer patients. We establish a significant positive correlation between IBM percentage and tumor–associate macrophages with a CCR2high/CD163high/CD206high/CD86lowprofile. Moreover, IBM expansion is associated with a decreased effector/regulatory T-cell ratio in ascites and with the presence of soluble immunosuppressive mediators. We also establish that IBM proportion positively correlates with the peritoneum tumor burden. Finally, the study of IBMs in patients with ovarian cancer under immunotherapy during the phase clinical trial supports IBMs to follow the evolution of tumor development and the treatment adaptation.Conclusions This study, which links IBM level with immunosuppression and tumor burden in peritoneum, identifies IBMs as apotential predictive signature of ascites immune status and as a biomarker ofovarian cancer development and treatment response.Trial registration number EudraCT: 2015-004252-22 NCT02978755. |
url |
https://jitc.bmj.com/content/8/1/e000472.full |
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