Pascual-García Mónica, Bértolo Cristina, Nieto Juan C, Serrat Neus, Espinosa Íñigo, D'Angelo Emanuela, Muñoz Raquel, Rovira Ramón, Vidal Silvia, Prat Jaime
Department of Pathology, Hospital de la Santa Creu i Sant Pau. Institute of Biomedical Research (IIB Sant Pau). Autonomous University of Barcelona, 08041 Barcelona, Spain.
Department of Immunology, Hospital de la Santa Creu i Sant Pau. Institute of Biomedical Research (IIB Sant Pau), 08041 Barcelona, Spain.
Hum Pathol. 2016 Oct;56:180-8. doi: 10.1016/j.humpath.2016.05.025. Epub 2016 Jun 23.
Carcinogenesis is a multistep process in which cancer cells and tumor stroma cells play important roles. T lymphocytes are immune constituents of tumor stroma and play a crucial function in anti-tumor response. By immunohistochemistry and flow cytometry, we studied T cytotoxic (CTLs) and T helper lymphocyte distribution and percentage in the tumor microenvironment and peripheral blood from 35 patients with endometrioid endometrial carcinomas (EEC). We also studied 23 healthy donors' blood samples as a control group. Tumor and non-tumoral endometrium samples were obtained. Immunohistochemistry revealed a high number of CTLs and T helper lymphocytes in the tumor stroma of myoinvasive EECs. T lymphocytes were mostly located in the invasive front. By flow cytometry, the percentages of CTLs and T helper lymphocytes were significantly higher in the tumor compared with the non-neoplastic endometrium (P = .0492 and P = .002). The mean fluorescence intensity of CD8 staining was lower in the tumor compared to the non-neoplastic endometrium (P = .001). There was also reduction of the mean fluorescence intensity of CD8 staining on peripheral blood from patients with grade 3 EECs compare to the peripheral blood from healthy donors (P = .0093). No alterations in the expression of granzymes A and B were found in the CTLs from the EEC cases. Finally, in a proteome profiler cytokine array we found that the growth differentiation factor 15 (GDF15) increased in blood in parallel to the tumor grade. EECs are capable of down-regulating CD8 expression of CTLs. Most likely, this effect is mediated by a soluble molecule present in plasma and is not a result of anergy or exhaustion state.
癌症发生是一个多步骤过程，其中癌细胞和肿瘤基质细胞发挥着重要作用。T淋巴细胞是肿瘤基质的免疫成分，在抗肿瘤反应中发挥关键作用。通过免疫组织化学和流式细胞术，我们研究了35例子宫内膜样子宫内膜癌（EEC）患者肿瘤微环境和外周血中细胞毒性T淋巴细胞（CTL）和辅助性T淋巴细胞的分布及百分比。我们还研究了23例健康供者的血样作为对照组。获取了肿瘤和非肿瘤性子宫内膜样本。免疫组织化学显示，肌层浸润性EECs的肿瘤基质中有大量CTL和辅助性T淋巴细胞。T淋巴细胞大多位于浸润前沿。通过流式细胞术，与非肿瘤性子宫内膜相比，肿瘤中CTL和辅助性T淋巴细胞的百分比显著更高（P = 0.0492和P = 0.002）。与非肿瘤性子宫内膜相比，肿瘤中CD8染色的平均荧光强度更低（P = 0.001）。与健康供者的外周血相比，3级EEC患者外周血中CD8染色的平均荧光强度也降低（P = 0.0093）。在EEC病例的CTL中未发现颗粒酶A和B表达的改变。最后，在蛋白质组分析细胞因子阵列中，我们发现生长分化因子15（GDF15）在血液中的增加与肿瘤分级平行。EEC能够下调CTL的CD8表达。最有可能的是，这种效应是由血浆中存在的一种可溶性分子介导的，而不是无反应性或耗竭状态的结果。
