RT Journal Article
SR Electronic
T1 Circulating CD14<sup>high</sup> CD16<sup>low</sup> intermediate blood monocytes as a biomarker of ascites immune status and ovarian cancer progression
JF Journal for ImmunoTherapy of Cancer
JO J Immunother Cancer
FD BMJ Publishing Group Ltd
SP e000472
DO 10.1136/jitc-2019-000472
VO 8
IS 1
A1 Mélissa Prat
A1 Augustin Le Naour
A1 Kimberley Coulson
A1 Fanny Lemée
A1 Hélène Leray
A1 Godefroy Jacquemin
A1 Mouna Chirine Rahabi
A1 Léa Lemaitre
A1 Hélène Authier
A1 Gwenaël Ferron
A1 Jean-Marc Barret
A1 Alejandra Martinez
A1 Maha Ayyoub
A1 Jean-Pierre Delord
A1 Laurence Gladieff
A1 Isabelle Tabah-Fisch
A1 Jean-François Prost
A1 Bettina Couderc
A1 Agnès Coste
YR 2020
UL http://jitc.bmj.com/content/8/1/e000472.abstract
AB 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.