Department of Gynaecology and Obstetrics, Centre for Integrated Oncology Bonn, Bonn University Medical Centre, Sigmund Freud-Str. 25, 53105, Bonn, Germany.
Cancer Immunol Immunother. 2010 Jun;59(6):909-19. doi: 10.1007/s00262-010-0817-1. Epub 2010 Jan 20.
Preoperative neoadjuvant chemotherapy (NAC) can significantly reduce tumour burden in patients with primarily unresectable chemosensitive tumours, allowing a more complete cytoreduction during debulking surgery and facilitating evaluation of tumour chemosensitivity, identification of appropriate treatment options and improvement of intervention protocols. In this study, we investigate, using immunohistochemistry, the impact of platinum/taxane-based NAC (NAC) on tumour-infiltrating lymphocytes (TILs) in advanced epithelial ovarian cancer (EOC) and their relationship with clinical outcome. All patients had clinical response, as shown by ascites volume and CA125 levels compared to pre-treatment findings. NAC intervention significantly increased CD4(+), CD8(+) and granzyme B(+) infiltration while Foxp3(+) accumulation remained unaffected. TILs were prognostically neutral for both progression-free survival (PFS) and overall survival (OS) before NAC. In contrast, after NAC, elevated granzyme B(+) infiltration displayed a tendency for improved PFS (log-rank 0.064). Further, low Foxp3(+) cell density was associated with longer PFS, as compared with strong Foxp3(+) infiltration (median 20.94 vs. 11.24 months; log-rank 0.0001) and with improved OS (median 30.75 vs. 16.04 months, respectively; log-rank 0.056), demonstrating clear prognostic significance for PFS. In addition, high granzyme B(+)/Foxp3(+) ratio post-NAC strongly correlated with improved PFS compared to low granzyme B(+)/Foxp3(+) cell ratio (median 17.88 vs. 11.24 months, respectively), and showed to be a favourable prognostic factor for PFS (log-rank 0.014). Our findings indicate that NAC elicited an immunologic profile in which low immunosuppressive Foxp3(+) infiltration and elevated numbers of activated granzyme B(+) cells were significantly associated with EOC-specific PFS, suggesting a contribution of immunologic effects to improved clinical outcome.
术前新辅助化疗（NAC）可以显著降低原发不可切除的化疗敏感肿瘤患者的肿瘤负荷，使在减瘤手术期间能够进行更完全的细胞减灭术，并有助于评估肿瘤化疗敏感性、确定合适的治疗选择和改进干预方案。在这项研究中，我们使用免疫组织化学方法研究了铂类/紫杉类为基础的 NAC（NAC）对晚期上皮性卵巢癌（EOC）肿瘤浸润淋巴细胞（TIL）的影响及其与临床结果的关系。所有患者均有临床反应，表现为腹水体积和 CA125 水平与治疗前相比有所降低。NAC 干预显著增加了 CD4(+)、CD8(+)和颗粒酶 B(+)的浸润，而 Foxp3(+)的积累则不受影响。在 NAC 之前，TIL 对无进展生存期（PFS）和总生存期（OS）的预后均为中性。相比之下，在 NAC 后，升高的颗粒酶 B(+)浸润有改善 PFS 的趋势（对数秩检验 0.064）。此外，与 Foxp3(+)细胞密度高相比，低 Foxp3(+)细胞密度与更长的 PFS 相关（中位数 20.94 与 11.24 个月；对数秩检验 0.0001），与 OS 改善相关（中位数 30.75 与 16.04 个月，对数秩检验 0.056），表明 PFS 的预后具有明显的意义。此外，NAC 后高 granzyme B(+)/Foxp3(+)比值与低 granzyme B(+)/Foxp3(+)细胞比值相比，与改善的 PFS 强烈相关（中位数 17.88 与 11.24 个月，对数秩检验 0.014），并显示为 PFS 的有利预后因素。我们的研究结果表明，NAC 引发了一种免疫表型，其中低免疫抑制性 Foxp3(+)浸润和活化的 granzyme B(+)细胞数量增加与 EOC 特异性 PFS 显著相关，表明免疫效应有助于改善临床结果。
