Study of the Role of the Tumor Microenvironment in Ovarian Cancer (MICO): A Prospective Monocentric Trial

ABSTRACT Background Ovarian cancer (OC) is one of the most aggressive tumors requiring new therapeutic approaches. Immunotherapy represents an opportunity, but to date, OC patients do not appear to benefit from current protocols. A better understanding of the composition of the tumor microenvironmen...

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Main Authors: Martina Arcieri, Eleonora Capezzali, Stefano Restaino, Sara Pregnolato, Laura Mariuzzi, Alessandro Mangogna, Maria Orsaria, Angelica Tulisso, Silvia Tonon, Maria De Martino, Miriam Isola, Lorenza Driul, Carlo Pucillo, Giovanni Scambia, Barbara Frossi, Giuseppe Vizzielli
Format: Article
Language:English
Published: Wiley 2025-06-01
Series:Cancer Reports
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Online Access:https://doi.org/10.1002/cnr2.70242
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author Martina Arcieri
Eleonora Capezzali
Stefano Restaino
Sara Pregnolato
Laura Mariuzzi
Alessandro Mangogna
Maria Orsaria
Angelica Tulisso
Silvia Tonon
Maria De Martino
Miriam Isola
Lorenza Driul
Carlo Pucillo
Giovanni Scambia
Barbara Frossi
Giuseppe Vizzielli
author_facet Martina Arcieri
Eleonora Capezzali
Stefano Restaino
Sara Pregnolato
Laura Mariuzzi
Alessandro Mangogna
Maria Orsaria
Angelica Tulisso
Silvia Tonon
Maria De Martino
Miriam Isola
Lorenza Driul
Carlo Pucillo
Giovanni Scambia
Barbara Frossi
Giuseppe Vizzielli
author_sort Martina Arcieri
collection DOAJ
description ABSTRACT Background Ovarian cancer (OC) is one of the most aggressive tumors requiring new therapeutic approaches. Immunotherapy represents an opportunity, but to date, OC patients do not appear to benefit from current protocols. A better understanding of the composition of the tumor microenvironment (TME), especially in its immune components, could unveil mechanisms of immune suppression in a useful way to predict response to therapies and develop new therapeutic approaches. Method The MICO (tumor MICroenvironment of Ovarian cancer) study is a single‐center observational study. Starting from peritoneal biopsy of high‐grade serous ovarian carcinoma (HGSOC), the purpose of the MICO study is to generate tumor patient‐derived organoid (PDOs) cultures and evaluate the concordance between in vitro platinum‐based chemotherapy sensitivity and in vivo sensitivity. Simultaneously, we will characterize through multiparameter cytofluorimetric analysis the composition of the OC TME, focusing on B lymphocytes and mast cells whose roles in ovarian cancer remain controversial and underinvestigated. Furthermore, patients experiencing recurrence will be longitudinally followed to monitor changes in the TME composition and the responsiveness of PDOs to in vitro stimulation with drugs. Discussion The association between the composition of the TME, the reactivity of the PDOs, and patients' disease progression will be analyzed to identify whether specific subpopulations of tumor‐infiltrating immune cells could be predictive factors of the disease outcomes. The comparison of molecular profiles, in vitro response to drugs, and clinical‐pathological data will allow the definition of a pattern capable of predicting the response of the primary tumor for the identification of those patients who may benefit from specific treatment. Strengths and Limitations The results of our study could help to better understand the OC behavior, may have implications for the development of effective immunotherapy and targeted pharmacological therapies for epithelial OC in a personalized medicine perspective. This will be a monocentric trial with an involvement of only 43 patients, so further studies will need to confirm our results. Trial Registration The clinical trial has been registered at Clinical‐Trials.gov with the identifier NCT06272240 on 02/14/2024
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spelling doaj-art-c8d847bc0e9e4293be65308d8f067a9c2025-06-26T07:14:52ZengWileyCancer Reports2573-83482025-06-0186n/an/a10.1002/cnr2.70242Study of the Role of the Tumor Microenvironment in Ovarian Cancer (MICO): A Prospective Monocentric TrialMartina Arcieri0Eleonora Capezzali1Stefano Restaino2Sara Pregnolato3Laura Mariuzzi4Alessandro Mangogna5Maria Orsaria6Angelica Tulisso7Silvia Tonon8Maria De Martino9Miriam Isola10Lorenza Driul11Carlo Pucillo12Giovanni Scambia13Barbara Frossi14Giuseppe Vizzielli15Clinic of Obstetrics and Gynecology “Santa Maria Della Misericordia” University Hospital, Azienda Sanitaria Universitaria Friuli Centrale Udine ItalyDepartment of Medicine (DMED) University of Udine Udine ItalyClinic of Obstetrics and Gynecology “Santa Maria Della Misericordia” University Hospital, Azienda Sanitaria Universitaria Friuli Centrale Udine ItalyDepartment of Medicine (DMED) University of Udine Udine ItalyDepartment of Medicine (DMED) University of Udine Udine ItalyDepartment of Medicine (DMED) University of Udine Udine ItalyInstitute of Pathology Academic Hospital Udine ItalyInstitute of Pathology Academic Hospital Udine ItalyDepartment of Medicine (DMED) University of Udine Udine ItalyDepartment of Medicine (DMED) University of Udine Udine ItalyDepartment of Medicine (DMED) University of Udine Udine ItalyClinic of Obstetrics and Gynecology “Santa Maria Della Misericordia” University Hospital, Azienda Sanitaria Universitaria Friuli Centrale Udine ItalyDepartment of Medicine (DMED) University of Udine Udine ItalyGynecologic Oncology Unit Fondazione “Policlinico Universitario A. Gemelli IRCCS,” Catholic University of the Sacred Heart Rome ItalyDepartment of Medicine (DMED) University of Udine Udine ItalyClinic of Obstetrics and Gynecology “Santa Maria Della Misericordia” University Hospital, Azienda Sanitaria Universitaria Friuli Centrale Udine ItalyABSTRACT Background Ovarian cancer (OC) is one of the most aggressive tumors requiring new therapeutic approaches. Immunotherapy represents an opportunity, but to date, OC patients do not appear to benefit from current protocols. A better understanding of the composition of the tumor microenvironment (TME), especially in its immune components, could unveil mechanisms of immune suppression in a useful way to predict response to therapies and develop new therapeutic approaches. Method The MICO (tumor MICroenvironment of Ovarian cancer) study is a single‐center observational study. Starting from peritoneal biopsy of high‐grade serous ovarian carcinoma (HGSOC), the purpose of the MICO study is to generate tumor patient‐derived organoid (PDOs) cultures and evaluate the concordance between in vitro platinum‐based chemotherapy sensitivity and in vivo sensitivity. Simultaneously, we will characterize through multiparameter cytofluorimetric analysis the composition of the OC TME, focusing on B lymphocytes and mast cells whose roles in ovarian cancer remain controversial and underinvestigated. Furthermore, patients experiencing recurrence will be longitudinally followed to monitor changes in the TME composition and the responsiveness of PDOs to in vitro stimulation with drugs. Discussion The association between the composition of the TME, the reactivity of the PDOs, and patients' disease progression will be analyzed to identify whether specific subpopulations of tumor‐infiltrating immune cells could be predictive factors of the disease outcomes. The comparison of molecular profiles, in vitro response to drugs, and clinical‐pathological data will allow the definition of a pattern capable of predicting the response of the primary tumor for the identification of those patients who may benefit from specific treatment. Strengths and Limitations The results of our study could help to better understand the OC behavior, may have implications for the development of effective immunotherapy and targeted pharmacological therapies for epithelial OC in a personalized medicine perspective. This will be a monocentric trial with an involvement of only 43 patients, so further studies will need to confirm our results. Trial Registration The clinical trial has been registered at Clinical‐Trials.gov with the identifier NCT06272240 on 02/14/2024https://doi.org/10.1002/cnr2.70242organoidsovarian cancertumor microenvironment
spellingShingle Martina Arcieri
Eleonora Capezzali
Stefano Restaino
Sara Pregnolato
Laura Mariuzzi
Alessandro Mangogna
Maria Orsaria
Angelica Tulisso
Silvia Tonon
Maria De Martino
Miriam Isola
Lorenza Driul
Carlo Pucillo
Giovanni Scambia
Barbara Frossi
Giuseppe Vizzielli
Study of the Role of the Tumor Microenvironment in Ovarian Cancer (MICO): A Prospective Monocentric Trial
Cancer Reports
organoids
ovarian cancer
tumor microenvironment
title Study of the Role of the Tumor Microenvironment in Ovarian Cancer (MICO): A Prospective Monocentric Trial
title_full Study of the Role of the Tumor Microenvironment in Ovarian Cancer (MICO): A Prospective Monocentric Trial
title_fullStr Study of the Role of the Tumor Microenvironment in Ovarian Cancer (MICO): A Prospective Monocentric Trial
title_full_unstemmed Study of the Role of the Tumor Microenvironment in Ovarian Cancer (MICO): A Prospective Monocentric Trial
title_short Study of the Role of the Tumor Microenvironment in Ovarian Cancer (MICO): A Prospective Monocentric Trial
title_sort study of the role of the tumor microenvironment in ovarian cancer mico a prospective monocentric trial
topic organoids
ovarian cancer
tumor microenvironment
url https://doi.org/10.1002/cnr2.70242
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