Bösmüller Hans-Christian, Wagner Philipp, Peper Janet Kerstin, Schuster Heiko, Pham Deborah Lam, Greif Karen, Beschorner Christine, Rammensee Hans-Georg, Stevanović Stefan, Fend Falko, Staebler Annette
*Institute of Pathology, and †Department of Obstetrics and Gynecology, University Hospital of Tübingen; ‡Department of Immunology, Institute of Cell Biology, University of Tübingen; and §German Cancer Consortium (DKTK), DKFZ partner site Tübingen, Tübingen, Germany.
Int J Gynecol Cancer. 2016 May;26(4):671-9. doi: 10.1097/IGC.0000000000000672.
Increased numbers of tumor-infiltrating lymphocytes (TILs) in high-grade serous ovarian cancer (HGSC) are associated with improved clinical outcome. Intraepithelial localization of TILs might be regulated by specific homing receptors, such as CD103, which is widely expressed by intraepithelial lymphocytes. Given the emerging role of CD103 TILs, we aimed to assess their contribution to the prognostic value of immunoscoring in HGSC.
The density of intratumoral CD3 and CD103 lymphocytes was examined by immunohistochemistry on a tissue microarray of a series of 135 patients with advanced HGSC and correlated with CD4, CD8, CD56, FoxP3, and TCRγ T-cell counts, as well as E-cadherin staining and conventional prognostic parameters and clinical outcome.
Both the presence of CD103 cells, as well as high numbers of intraepithelial CD3 lymphocytes (CD3E), showed a significant correlation with overall survival, in the complete series, as well as in patients with optimal debulking and/or platinum sensitivity. Combining CD3 and CD103 counts improved prognostication and identified 3 major subgroups with respect to overall survival. The most pronounced effect was demonstrated for patients with optimally resected and platinum-sensitive tumors. Patients with CD3/CD103 tumors showed a 5-year survival rate at 90%, CD3/CD103 at 63%, and CD3/CD103 at 0% (P < 0.001).
These results suggest that combined assessment of CD103 and CD3 counts improves the prognostic value of TIL counts in HGSC and might identify patients with early relapse or long-term survival based on the type and extent of the immune response.
高级别浆液性卵巢癌(HGSC)中肿瘤浸润淋巴细胞(TILs)数量增加与临床结局改善相关。TILs的上皮内定位可能受特定归巢受体调控,如CD103,上皮内淋巴细胞广泛表达该受体。鉴于CD103⁺ TILs的新作用,我们旨在评估其对HGSC免疫评分预后价值的贡献。
通过免疫组化在135例晚期HGSC患者的组织微阵列上检测瘤内CD3和CD103淋巴细胞密度,并与CD4、CD8、CD56、FoxP3和TCRγ T细胞计数以及E-钙黏蛋白染色、传统预后参数和临床结局相关联。
在整个队列以及减瘤满意和/或铂敏感的患者中,CD103⁺细胞的存在以及大量上皮内CD3淋巴细胞(CD3E)均与总生存期显著相关。结合CD3和CD103计数可改善预后评估,并确定了3个总生存期主要亚组。在减瘤满意且铂敏感的肿瘤患者中效果最为显著。CD3⁺/CD103⁺肿瘤患者的5年生存率为90%,CD3⁺/CD103⁻为63%,CD3⁻/CD103⁻为0%(P<0.001)。
这些结果表明,联合评估CD103和CD3计数可提高HGSC中TIL计数的预后价值,并可能根据免疫反应的类型和程度识别早期复发或长期生存的患者。