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