Koyama S, Maruyama T, Adachi S, Nozue M
Department of Internal Medicine, Institute of Clinical Medicine, University of Tsukuba, Tsukuba-City, Ibaraki, Japan.
J Cancer Res Clin Oncol. 1998;124(7):383-8. doi: 10.1007/s004320050187.
Costimulation of T cells via B7-1 and B7-2 molecules on a tumor has been shown to be important for eliciting cell-mediated antitumor immunity. We studied the surface expression of B7-1 and B7-2 in 24 cases of gastric carcinoma from the primary locus, 20 cases of metastatic carcinoma from malignant ascites, 20 cases of benign gastric mucosa and 7 gastric carcinoma cell lines by two-color flow cytometry with mAb CD80 and CD86. The B7-1 and B7-2 molecules were expressed by 6 cell lines, and 1 cell line showed the predominant expression of B7-2 but not B7-1. Almost all patients with primary gastric carcinoma and benign gastric mucosa showed high levels of expression of the B7-1 and B7-2, revealing approximately 40%-60% positive cells. However, the percentage of B7-1-positive cells of poorly differentiated primary carcinomas was significantly lower than that of well-differentiated carcinoma and normal mucosa (P < 0.01). Furthermore, all of the metastatic carcinoma cells revealed consistently very low or undetectable levels of expression of the B7-1 molecule, only 8% (mean) of cells being positive, despite showing higher levels of B7-2 expression. Thus, it seems likely that decreased or deleted expression of B7-1 correlates with the grade of tumor differentiation, tumor progression and metastasis. These results suggest that the B7-1 molecule on the gastric carcinoma bearing CD80+CD86+ is abrogated during tumor invasion and/or metastasis, and the tumor finally acquires the CD80-CD86+ phenotype. Consequently, inadequate B7-1 costimulation may contribute to the escape of tumors from destruction by the host's immune system.
肿瘤上的B7-1和B7-2分子对T细胞的共刺激已被证明对于引发细胞介导的抗肿瘤免疫很重要。我们通过用单克隆抗体CD80和CD86进行双色流式细胞术，研究了24例原发性胃癌、20例恶性腹水转移癌、20例良性胃黏膜以及7种胃癌细胞系中B7-1和B7-2的表面表达情况。6种细胞系表达B7-1和B7-2分子，1种细胞系显示B7-2的主要表达而无B7-1表达。几乎所有原发性胃癌和良性胃黏膜患者均显示B7-1和B7-2的高表达水平，阳性细胞约为40%-60%。然而，低分化原发性癌的B7-1阳性细胞百分比显著低于高分化癌和正常黏膜（P<0.01）。此外，所有转移癌细胞均显示B7-1分子的表达持续非常低或无法检测到，尽管B7-2表达水平较高，但只有8%（平均）的细胞为阳性。因此，B7-1表达的降低或缺失似乎与肿瘤分化程度、肿瘤进展和转移相关。这些结果表明，携带CD80+CD86+的胃癌上的B7-1分子在肿瘤侵袭和/或转移过程中被消除，肿瘤最终获得CD80-CD86+表型。因此，B7-1共刺激不足可能导致肿瘤逃避宿主免疫系统的破坏。
