胃癌局部微环境中细胞免疫功能状况与预后的关系

Relationship between cellular immune function and prognosis in the microenvironment of gastric cancer

目的：检测胃癌患者肿瘤、瘤旁、正常胃壁组织（瘤旁7～8 cm）Treg细胞和多种免疫细胞密度及功能状况，分析其与患者临床病理和预后的关系。方法采用免疫组织化学方法检测200例胃癌手术患者肿瘤、瘤旁1 cm、瘤旁正常胃壁组织中Treg细胞和多种免疫细胞密度及功能状况，利用多种统计学方法，了解 Treg 细胞与多种免疫细胞间的关系及其与患者临床病理和预后的关系。结果（1）胃癌肿瘤中Treg细胞和CD3、CD4、CD8、NK细胞、DC阳性细胞的平均浸润数目高于正常胃壁组织（P≤0.05），而肿瘤与瘤旁1 cm之间的免疫细胞数目无统计学差异（P≥0.05）。（2）在肿瘤组织中CD8、NK细胞、DC 阳性细胞低浸润组较之高浸润组在区域淋巴结转移方面有统计学差异（P＜0.05），但对肿瘤的复发转移和总生存期无明显影响。（3）在肿瘤组织中Treg细胞低浸润组较之高浸润组在TNM分期高低（P＞0.001），肿瘤复发转移（P＝0.048）和生存情况（P＝0.021）有统计学差异。Cox单因素（P＝0.012）和多因素生存分析（P＝0.0035）提示Treg是胃癌患者独立预后因素。结论在胃癌肿瘤局部聚集着比正常组织内更多的各类免疫细胞，其中CD8、NK细胞、DC细胞在肿瘤局部更高的浸润度可以减少区域淋巴结转移，但对患者最终预后无影响；真正对胃癌预后生存有影响的是肿瘤组织中Treg细胞的浸润情况。它可以作为胃癌抗肿瘤免疫治疗的靶点。

Objective To obtain results about the relationship between Treg cells and a variety of immune cells with the clinical pathology and prognosis, We detected tumor, normal gastric tissues, adjacent to the tumor and in patients with gastric cancer and investigated the density, position and function about Treg cells and a variety of immune cell. Methods The 200 cases was detected by immunohistochemical method with tumor, peritumoral 1 cm, normal gastric tissues and for density and function about Treg cells and a variety of immune cell.Through statistical methods of t test, chi-square test, Cox survival analysis, we understand the relationship between Treg cells and a variety of immune cells with clinical pathology and prognosis. Results （1）The average number of gastric cancer tumor infiltration of Treg cells and CD3, CD4, CD8, NK cells, DC positive cells was higher than that of 7-8 cm （normal gastric tissues adjacent to the tumor） （P≤0.05）, but there was no difference between the number of tumors and adjacent 1cm immune cells （P≥0.05）. （2）CD8, NK cells and DC positive cells with low infiltration group in the tumor tissue have significant difference in the regional lymph node metastasis than in the high infiltration group（P〈0.05）, but had no significant effect on recurrence and overall survival. （3）In the tumor tissue, between Treg cells with low infiltration group and high infiltration group, there were significant differences in the TNM stage（P〉0.001）, recurrence and metastasis of tumor （P=0.048） and survival（P=0.021）. Single（P=0.012） and multivariate Cox survival analysis（P=0.0035） indicated that the Treg was the independent prognostic factor. Conclusions In the gastric tumor, there were more various types of immune cells than in normal tissues, including higher infiltration of CD8, NK cells and DC cells .They can reduce regional lymph node metastasis, but had no effect on the final outcome for the patient.The real impact on the prognosis of gastric cancer survival is the infiltration of Treg cells in tumor tissue.It can be as targets for cancer immunotherapy against tumors.