Department of Digestive Surgery, and Breast and Thyroid Surgery, Kagoshima University School of Medicine, 8-35-1 Sakuragaoka, Kagoshima 890-8520, Japan.
Cancer Immunol Immunother. 2012 Oct;61(10):1663-9. doi: 10.1007/s00262-012-1225-5. Epub 2012 Feb 29.
Since antitumor immune reactions between tumors and intratumoral immunocytes have been verified in several human tumors, immunological therapeutic strategies must be considered to obtain the proper efficacy of tumor shrinkage under these conditions. Human leukocyte antigen (HLA) class I expression in cancer cells and degree of infiltration of regulatory T cells (Tregs) in the stroma have been regarded as important markers of antitumor immune reactions in the context of independent immunological mechanisms. In the current study, we investigated HLA class I expression and Treg cells infiltration in gastric cancer and discussed the clinical implications of this combinatory analysis in gastric cancer.
A total of 141 gastric cancer patients who received R0 gastrectomy at Kagoshima University Hospital were studied. Immunohistochemically, in 141 gastric cancer patients, HLA class I expression and Treg cell infiltration in cancerous tissue were evaluated using HLA class I (EMR8-5) and forkhead box p3 (FOXP3) monoclonal antibodies. The correlation between clinical factors and tumor-infiltrating Treg cells was analyzed.
HLA class I expression was positively associated with depth of tumor invasion (P < 0.05). Infiltration of Foxp3-positive cells did not correlate with any clinicopathological markers. HLA class I expression had no association with Treg cell infiltration (r = 0.04). A better postoperative outcome was associated with fewer numbers of Treg infiltration (P = 0.034). A combination of HLA and Treg analysis may lead to a more accurate prediction of postoperative outcome (P = 0.02).
Two different antitumor immunological markers, Treg infiltration and HLA class I expression, affected clinicopathological factors in gastric cancer by different mechanisms. Thus, an immunological combination of HLA class I expression and Treg cell infiltration may more accurately predict postoperative outcome. Immunological balance needs to be restored after evaluation of each immunological deficit in gastric cancer.
在几种人类肿瘤中已经证实了肿瘤与肿瘤内免疫细胞之间的抗肿瘤免疫反应，因此必须考虑免疫治疗策略，以在这些条件下获得适当的肿瘤缩小效果。在独立的免疫机制背景下，癌细胞中人类白细胞抗原（HLA）I 类表达和基质中调节性 T 细胞（Treg）的浸润程度已被认为是抗肿瘤免疫反应的重要标志物。在本研究中，我们研究了胃癌中的 HLA I 类表达和 Treg 细胞浸润，并讨论了这种组合分析在胃癌中的临床意义。
对在鹿儿岛大学医院接受 R0 胃切除术的 141 例胃癌患者进行了研究。使用 HLA I 类（EMR8-5）和叉头框 P3（FOXP3）单克隆抗体，通过免疫组织化学方法对 141 例胃癌患者的癌组织中 HLA I 类表达和 Treg 细胞浸润进行评估。分析了临床因素与肿瘤浸润 Treg 细胞之间的相关性。
HLA I 类表达与肿瘤浸润深度呈正相关（P<0.05）。Foxp3 阳性细胞浸润与任何临床病理标志物均无相关性。HLA I 类表达与 Treg 细胞浸润无相关性（r=0.04）。术后结局较好与 Treg 浸润细胞数量较少有关（P=0.034）。HLA 和 Treg 分析的组合可能导致更准确地预测术后结局（P=0.02）。
两种不同的抗肿瘤免疫标志物，Treg 浸润和 HLA I 类表达，通过不同的机制影响胃癌的临床病理因素。因此，HLA I 类表达和 Treg 细胞浸润的免疫组合可能更准确地预测术后结局。需要在评估胃癌中每种免疫缺陷后恢复免疫平衡。
