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B 细胞对高级别浆液性卵巢癌的预后至关重要。

B cells critical for outcome in high grade serous ovarian carcinoma.

机构信息

Department of Obstetrics and Gynecology, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands.

Department of Radiotherapy, Erasmus University Medical Center, Rotterdam, The Netherlands.

出版信息

Int J Cancer. 2024 Dec 15;155(12):2265-2276. doi: 10.1002/ijc.35149. Epub 2024 Aug 22.

Abstract

Recent work has shown evidence for the prognostic significance of tumor infiltrating B cells (B-TIL) in high grade serous ovarian carcinoma (HGSOC), the predominant histological subtype of ovarian cancer. However, it remains unknown how the favorable prognosis associated with B-TIL relates to the current standard treatments of primary debulking surgery (PDS) followed by chemotherapy or (neo-)adjuvant chemotherapy (NACT) combined with interval debulking surgery. To address this, we analyzed the prognostic impact of B-TIL in relationship to primary treatment and tumor infiltrating T cell status in a highly homogenous cohort of HGSOC patients. This analysis involved a combined approach utilizing histological data and high-dimensional flow cytometry analysis. Our findings indicate that while HGSOC tumors pre-treated with NACT are infiltrated with tumor-reactive CD8 and CD4 TIL subsets, only B-TIL and IgA plasma blasts confer prognostic benefit in terms of overall survival. Importantly, the prognostic value of B-TIL and IgA plasma blasts was not restricted to patients treated with NACT, but was also evident in patients treated with PDS. Together, our data point to a critical prognostic role for B-TIL in HGSOC patients independent of T cell status, suggesting that alternative treatment approaches focused on the activation of B cells should be explored for HGSOC.

摘要

最近的研究表明,肿瘤浸润 B 细胞(B-TIL)在高级别浆液性卵巢癌(HGSOC)中具有预后意义,HGSOC 是卵巢癌的主要组织学亚型。然而,目前尚不清楚与 B-TIL 相关的有利预后与原发性减瘤手术(PDS)后化疗或(新)辅助化疗(NACT)联合间隔性减瘤手术之间的关系。为了解决这个问题,我们分析了 B-TIL 在高度同质的 HGSOC 患者群体中与原发性治疗和肿瘤浸润 T 细胞状态的关系的预后影响。这项分析采用了结合组织学数据和高维流式细胞术分析的综合方法。我们的研究结果表明,虽然接受 NACT 预处理的 HGSOC 肿瘤浸润了肿瘤反应性 CD8 和 CD4 TIL 亚群,但只有 B-TIL 和 IgA 浆细胞才能在总体生存方面带来预后获益。重要的是,B-TIL 和 IgA 浆细胞的预后价值不仅限于接受 NACT 治疗的患者,在接受 PDS 治疗的患者中也同样明显。总之,我们的数据表明,B-TIL 在 HGSOC 患者中具有关键的预后作用,与 T 细胞状态无关,这表明应探索针对 HGSOC 的侧重于 B 细胞激活的替代治疗方法。

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