Jäntti Tiina, Luhtala Satu, Mäenpää Johanna, Staff Synnöve
Faculty of Medicine and Health Technology, University of Tampere, Tampere, Finland.
Department of Pathology, Seinäjoki Central Hospital, Seinäjoki, Finland.
Tumour Biol. 2020 Nov;42(11):1010428320971404. doi: 10.1177/1010428320971404.
Ovarian cancer is the most lethal of gynecological cancers with 5-year survival rate of ca. 45%. The most common histologic subtype is high-grade serous carcinoma, which typically is presented with advanced stage and development of chemoresistance. Therefore, new treatment options, including immunotherapies, are needed. Understanding the features of the immune cell populations in the tumor microenvironment is essential for developing personalized treatments and finding predictive biomarkers. Digital image analysis may enhance the accuracy and reliability of immune cell infiltration assessment in the tumor microenvironment. The aim of this study was to characterize tumor microenvironment in a retrospective cohort of high-grade serous carcinoma samples with whole-slide imaging and digital image analysis. Formalin-fixed paraffin-embedded high-grade serous carcinoma tumor tissue samples (n = 67) were analyzed for six immunohistochemical stainings: CD4, CD8, FoxP3, granzyme B, CD68, and CD163. The stained sample slides were scanned into a digital format and assessed using QuPath 0.1.2 and ImageJ software. Staining patterns were associated with clinicopathological data. The higher numbers of intraepithelial CD8+, CD163+, and granzyme B+ immune cells were associated with survival benefit when analyzed individually, while high levels of both CD8+ and granzyme B+ tumor-infiltrating lymphocytes were an independent prognostic factor in the Cox multivariate regression analysis (median progression-free survival; hazard ratio = 0.287, p = 0.002). Specimens taken after administration of neoadjuvant chemotherapy presented with lower FoxP3+ tumor-infiltrating lymphocyte density (Fisher's exact test, p = 0.013). However, none of the studied immunomarkers was associated with overall survival or clinical factors. Tumors having high amount of both intraepithelial CD8+ and granzyme B+ tumor-infiltrating lymphocytes showed better progression-free survival, possibly reflecting an activated immune state in the tumor microenvironment. The combined positivity of CD8 and granzyme B warrants further investigation with respect to predicting response to immune therapy. Neoadjuvant chemotherapy may have an effect on the tumor microenvironment and therefore on the response to immuno-oncologic or chemotherapy treatments.
卵巢癌是最致命的妇科癌症，5年生存率约为45%。最常见的组织学亚型是高级别浆液性癌，通常表现为晚期且会产生化疗耐药性。因此，需要新的治疗选择，包括免疫疗法。了解肿瘤微环境中免疫细胞群体的特征对于开发个性化治疗方案和寻找预测性生物标志物至关重要。数字图像分析可以提高肿瘤微环境中免疫细胞浸润评估的准确性和可靠性。本研究的目的是通过全切片成像和数字图像分析对高级别浆液性癌样本的回顾性队列中的肿瘤微环境进行特征描述。对67例福尔马林固定石蜡包埋的高级别浆液性癌肿瘤组织样本进行了六种免疫组织化学染色分析：CD4、CD8、FoxP3、颗粒酶B、CD68和CD163。将染色后的样本玻片扫描成数字格式，并使用QuPath 0.1.2和ImageJ软件进行评估。染色模式与临床病理数据相关。单独分析时，上皮内CD8+、CD163+和颗粒酶B+免疫细胞数量较多与生存获益相关，而在Cox多变量回归分析中，高水平的CD8+和颗粒酶B+肿瘤浸润淋巴细胞是一个独立的预后因素（无进展生存期中位数；风险比=0.287，p=0.002）。新辅助化疗后采集的标本中FoxP3+肿瘤浸润淋巴细胞密度较低（Fisher精确检验，p=0.013）。然而，所研究的免疫标志物均与总生存期或临床因素无关。上皮内CD8+和颗粒酶B+肿瘤浸润淋巴细胞数量均较高的肿瘤显示出更好的无进展生存期，这可能反映了肿瘤微环境中的激活免疫状态。CD8和颗粒酶B的联合阳性在预测免疫治疗反应方面值得进一步研究。新辅助化疗可能对肿瘤微环境有影响，因此对免疫肿瘤学或化疗治疗的反应也有影响。
