Lalos Alexandros, Neri Ornella, Ercan Caner, Wilhelm Alexander, Staubli Sebastian, Posabella Alberto, Weixler Benjamin, Terracciano Luigi, Piscuoglio Salvatore, Stadlmann Sylvia, Spagnoli Giulio C, Droeser Raoul A, Singer Gad
University Center for Gastrointestinal and Liver Diseases, Clarunis, University of Basel, 4031 Basel, Switzerland.
Institute of Pathology, University Hospital Basel, 4056 Basel, Switzerland.
Cancers (Basel). 2021 Nov 18;13(22):5783. doi: 10.3390/cancers13225783.
Ovarian cancer (OC) is the most aggressive and fatal malignancy of the female reproductive system. Debulking surgery with adjuvant chemotherapy represents the standard treatment, but recurrence rates are particularly high. Over the past decades, the association between the immune system and cancer progression has been extensively investigated. However, the interaction between chemotherapy and cancer immune infiltration is still unclear. In this study, we examined the prognostic role of CD16 expression in OC, as related to the effectiveness of standard adjuvant chemotherapy treatment.
We analyzed the infiltration by immune cells expressing CD16, a well-characterized natural killer (NK) and myeloid cell marker, in a tissue microarray (TMA) of 47 patient specimens of primary OCs and their matching recurrences by immunohistochemistry (IHC). We analyzed our data first in the whole cohort, then in the primary tumors, and finally in recurrences. We focused on recurrence-free survival (RFS), overall survival (OS), and chemosensitivity. Chemosensitivity was defined as RFS of more than 6 months.
There was no significant correlation between CD16 expression and prognosis in primary carcinomas. However, interestingly, a high density of CD16-expressing tumor-infiltrating immune cells (TICs) in recurrent carcinoma was associated with better RFS ( = 0.008) and OS ( = 0.029). Moreover, high CD16 cell density in recurrent ovarian carcinoma showed a significant association with chemosensitivity ( = 0.034). Univariate Cox regression analysis revealed that the high expression of CD16+ TIC in recurrent cancer biopsies is significantly associated with an increased RFS (HR = 0.49; 95% CI 0.24-0.99; = 0.047) and OS (HR = 0.28; 95% CI 0.10-0.77; = 0.013). However, this was not independent of known prognostic factors such as age, FIGO stage, resection status, and the number of chemotherapy cycles.
The high density of CD16-expressing TICs in recurrent ovarian cancer is associated with a better RFS and OS, thereby suggesting a previously unsuspected interaction between standard OC chemotherapy and immune cell infiltration.
卵巢癌（OC）是女性生殖系统中最具侵袭性和致命性的恶性肿瘤。减瘤手术联合辅助化疗是标准治疗方法，但复发率特别高。在过去几十年中，免疫系统与癌症进展之间的关联已得到广泛研究。然而，化疗与癌症免疫浸润之间的相互作用仍不清楚。在本研究中，我们研究了CD16表达在OC中的预后作用，这与标准辅助化疗治疗的有效性相关。
我们通过免疫组织化学（IHC）分析了47例原发性OC患者标本及其匹配复发组织的组织微阵列（TMA）中表达CD16的免疫细胞的浸润情况，CD16是一种特征明确的自然杀伤（NK）细胞和髓样细胞标志物。我们首先在整个队列中分析数据，然后在原发性肿瘤中分析，最后在复发肿瘤中分析。我们关注无复发生存期（RFS）、总生存期（OS）和化疗敏感性。化疗敏感性定义为RFS超过6个月。
原发性癌中CD16表达与预后无显著相关性。然而，有趣的是，复发性癌中表达CD16的肿瘤浸润免疫细胞（TICs）高密度与更好的RFS（P = 0.008）和OS（P = 0.029）相关。此外，复发性卵巢癌中高CD16细胞密度与化疗敏感性显著相关（P = 0.034）。单因素Cox回归分析显示，复发性癌症活检中CD16 + TIC的高表达与RFS增加显著相关（HR = 0.49；95%CI 0.24 - 0.99；P = 0.047）和OS（HR = 0.28；95%CI 0.10 - 0.77；P = 0.013）。然而，这并非独立于年龄、国际妇产科联盟（FIGO）分期、切除状态和化疗周期数等已知预后因素。
复发性卵巢癌中表达CD16的TICs高密度与更好的RFS和OS相关，从而提示标准OC化疗与免疫细胞浸润之间存在此前未被怀疑的相互作用。
