髓系细胞网络控制复发性卵巢癌原始免疫景观的重建，这一成果由洛桑大学Denarda Dangaj Laniti课题组经过不懈努力而取得。该项研究成果发表在2025年7月31日出版的《癌细胞》上。

该课题组研究人员分析了来自5个独立队列的595名OC患者的697个肿瘤样本（566个原发和131个复发），捕获肿瘤浸润淋巴细胞（TIL）异质性，并确定其与预后和TIL相关的免疫表型：髓系网络驱动恶性进展。该研究团队发现，在临床前motheme模型中，与发炎的人类OCs类似，复发的Brca1mut肿瘤维持激活的TILs：树突状细胞（DCs）壁龛，但通过上调COX/PGE2信号传导逃避免疫控制。相反，复发的Brca1wt肿瘤表现出TILs:DCs小生境的缺失和积累的免疫抑制肿瘤微环境（TME）网络，其特征是Trem2/ApoEhigh的肿瘤相关巨噬细胞（TAMs）和Nduf4l2high/Galectin3high的恶性状态。复发性肿瘤再现了原发肿瘤的免疫原性特征。他们的发现揭示了Brca依赖性TIL：髓系串音是复发性OC持续免疫原性的关键，并提出了提高化疗疗效的新靶点。

据悉，免疫疗法在复发性卵巢癌（OC）中显示出有限的成功，其预后见解主要来自于未经治疗的肿瘤。

附：英文原文

Title: Myeloid cell networks govern re-establishment of original immune landscapes in recurrent ovarian cancer

Author: Eleonora Ghisoni, Fabrizio Benedetti, Aspram Minasyan, Mathieu Desbuisson, Paula Cunnea, Alizée J. Grimm, Noémie Fahr, Charlotte Capt, Nicolas Rayroux, Flavia De Carlo, Doga C. Gulhan, Julien Dagher, David Barras, Matteo Morotti, Juan A. Marín-Jiménez, Bovannak Stewen Chap, Tania Santoro, Giulia Spagnol, Mapi Fleury, Katerina Fortis, Julien Dorier, Mary K. Townsend, Stephanie Tissot, Sylvie Rusakiewicz, Humberto J. Ferreira, Anne I. Kraemer, Michal Bassani-Stenberg, Elizabeth M. Swisher, Lana A. Kandalaft, Spyridon A. Mastroyannis, Kathleen T. Montone, Daniel J. Powell, Susana Banerjee, Kathryn L. Terry, Shelley S. Tworoger, Mikal J. Pittet, Janos L. Tanyi, George Coukos, Melissa A. Merritt, Christina Fotopoulou, Jose R. Conejo-Garcia, Denarda Dangaj Laniti

Issue&Volume: 2025-07-31

Abstract: Immunotherapy has shown limited success in recurrent ovarian cancer (OC), with prognostic insights largely derived from treatment-naive tumors. We analyzed 697 tumor samples (566 primary and 131 recurrent) from 595 OC patients across five independent cohorts, capturing tumor-infiltrating lymphocytes (TILs) heterogeneity and identifying four immune phenotypes linked to prognosis and TIL:myeloid networks driving malignant progression. We found that in preclinical mouse models, mirroring inflamed human OCs, the recurrent Brca1mut tumors maintained activated TILs:dendritic cells (DCs) niches but evaded immune control through upregulation of COX/PGE2 signaling. Conversely, recurrent Brca1wt tumors displayed loss of TILs:DCs niches and accumulated immunosuppressive tumor microenvironment (TME) networks featuring Trem2/ApoEhigh tumor associated macrophages (TAMs) and Nduf4l2high/Galectin3high malignant states. Recurrent tumors recapitulate the immunogenic landscapes of original cancers. Our findings reveal BRCA-dependent TIL:myeloid crosstalk as key to persistent immunogenicity in recurrent OC and propose new targets to enhance chemotherapy efficacy.

DOI: 10.1016/j.ccell.2025.07.005

Source: https://www.cell.com/cancer-cell/abstract/S1535-6108(25)00276-4