肿瘤微环境在卵巢癌（MICO）中的作用研究：一项前瞻性单中心试验

IF 1.5 Q4 ONCOLOGY

Cancer reports Pub Date : 2025-06-04 DOI:10.1002/cnr2.70242

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

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引用次数: 0

摘要

卵巢癌（OC）是最具侵袭性的肿瘤之一，需要新的治疗方法。免疫疗法代表了一个机会，但到目前为止，卵巢癌患者似乎并没有从目前的治疗方案中获益。更好地了解肿瘤微环境（TME）的组成，特别是其免疫成分，可以揭示免疫抑制的机制，以有效的方式预测对治疗的反应并开发新的治疗方法。方法MICO （tumor MICroenvironment of Ovarian cancer）研究为单中心观察性研究。MICO研究从高级别浆液性卵巢癌（HGSOC）的腹膜活检开始，目的是产生肿瘤患者来源的类器官（PDOs）培养物，并评估体外铂类化疗敏感性与体内敏感性之间的一致性。同时，我们将通过多参数细胞荧光分析来表征OC TME的组成，重点关注B淋巴细胞和肥大细胞，它们在卵巢癌中的作用仍然存在争议和研究不足。此外，将对复发患者进行纵向随访，以监测TME成分的变化以及pdo对体外药物刺激的反应性。将分析TME的组成、pdo的反应性和患者疾病进展之间的关系，以确定肿瘤浸润免疫细胞的特定亚群是否可能是疾病结局的预测因素。分子谱、体外药物反应和临床病理数据的比较将允许定义一种模式，能够预测原发肿瘤的反应，从而确定那些可能从特定治疗中受益的患者。我们的研究结果有助于更好地理解上皮性OC的行为，可能对从个性化医学角度开发有效的免疫治疗和靶向药物治疗上皮性OC具有启示意义。这将是一项仅涉及43名患者的单中心试验，因此需要进一步的研究来证实我们的结果。该临床试验已于2024年2月14日在clinical - trials .gov注册，注册号为NCT06272240

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

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.