Department of Radiation Oncology, University Hospital Friedrich-Alexander-University of Erlangen-Nuremberg, Universitätsstr. 27, 91054, Erlangen, Germany.
Virchows Arch. 2011 Apr;458(4):403-11. doi: 10.1007/s00428-011-1058-1. Epub 2011 Feb 26.
Tumor-infiltrating lymphocytes (TILs) in gastric adenocarcinoma show a strong compartmentalization with high numbers of lymphocytes in the stroma and low intraepithelial lymphocyte counts. Our previous study has shown stromal regulatory T cells (Treg) to be associated with a beneficial outcome in intestinal type cancer of the cardia. We undertook the present study to further evaluate the immunogenic and inflammatory environment in intestinal-type gastric adenocarcinoma of the cardia. We assessed CXCR3 expression, Epstein-Barr virus (EBV) status, Her2/ERBB2 status and overexpression/amplification using tissue microarrays (immunohistochemistry and in situ hybridization) of 52 patients. The data were correlated to different TIL subset counts (CD3, CD8, GranzymeB, FoxP3 and CD20) and to infiltrating histiocytes (CD68) both in the tumor and the surrounding stromal tissue that were reported earlier. Her2/ERBB2 overexpression/amplification showed no correlation to tumor stage. Moreover, for the first time, we show here that Her2/ERBB2 overexpression/amplification has no correlation to overall or subset-specific TIL infiltration. EBV infection was seen in four cases and showed a strong association with intratumoral CD8(+) T cell infiltration as well as a moderate correlation to stromal CD8(+) T cell accumulation. Intratumoral CD8(+) T cell infiltration was significantly correlated to intratumoral FoxP3(+) Treg infiltration, and to a lesser extent, to stromal FoxP3(+) Treg counts. Stromal CXCR3(+) T cell infiltration showed an inverse correlation to T category. This highlights the importance of stromal immune processes for cancer growth and suggests a subversion of Th1 immunoresponse in cancer progression and underlines the important role of inflammation for early carcinogenesis.
胃腺癌中的浸润淋巴细胞（TILs）表现出强烈的区室化，基质中有大量淋巴细胞，上皮内淋巴细胞计数较低。我们之前的研究表明，间质调节性 T 细胞（Treg）与贲门肠型胃癌的良好预后相关。我们进行了本研究，以进一步评估贲门肠型胃腺癌的免疫原性和炎症环境。我们使用组织微阵列（免疫组织化学和原位杂交）评估了 52 例患者的 CXCR3 表达、Epstein-Barr 病毒（EBV）状态、Her2/ERBB2 状态和过表达/扩增。数据与不同的 TIL 亚群计数（CD3、CD8、GranzymeB、FoxP3 和 CD20）以及先前报道的肿瘤和周围基质组织中的浸润组织细胞（CD68）相关。Her2/ERBB2 过表达/扩增与肿瘤分期无关。此外，我们首次表明，Her2/ERBB2 过表达/扩增与总体或特定 TIL 浸润无关。在四个病例中观察到 EBV 感染，与肿瘤内 CD8(+)T 细胞浸润有很强的相关性，与基质 CD8(+)T 细胞积聚有中度相关性。肿瘤内 CD8(+)T 细胞浸润与肿瘤内 FoxP3(+)Treg 浸润显著相关，与基质 FoxP3(+)Treg 计数相关性较小。基质 CXCR3(+)T 细胞浸润与 T 分期呈负相关。这突出了基质免疫过程对癌症生长的重要性，并表明 Th1 免疫反应在癌症进展中被颠覆，并强调了炎症在早期癌变中的重要作用。
