de Jong W H, Teppema J S, Wagenaar S S, Paques M, Steerenberg P A, Ruitenberg E J
Virchows Arch B Cell Pathol Incl Mol Pathol. 1986;50(3):249-69. doi: 10.1007/BF02889905.
The histology of immunologically mediated tumor regression was studied in the syngenic strain 2 guinea pig/line 10 hepatocellular carcinoma tumor system. Tumor regression was induced non-specifically by the intralesional injection of living Bacillus Calmette-Guérin (BCG) in 7-day-old established tumors (diameter 8-10 mm). In untreated line 10 tumors at day 7 a mild to moderate inflammatory reaction was present, which consisted mainly of small mononuclear cells; in addition large mononuclear cells and basophils were present. Intratumoral BCG-treatment induced a prominent increase in the inflammatory reaction due to an influx of small and large mononuclear cells and neutrophils. Small mononuclear cells were identified mainly as lymphocytes whereas large mononuclear cells belonged mainly to the macrophage line. Intratumoral administration of BCG resulted in a granulomatous reaction. A time-related decrease in the number of tumor cells and an increase in inflammation, associated with purulent lysis of the granulomatous tissue, was observed. Specific immune-mediated tumor rejection occurred in animals both after active immunization and after adoptive transfer of immune spleen cells. In actively immunized animals the tumor cells were rapidly rejected and from day 4 onwards no tumor cells could be detected at the injection site. Lymphocytes were the major component of the inflammatory reaction; large mononuclear cells were present to a lesser extent and basophilic granulocytes were regularly observed. After adoptive transfer of immunity with immune spleen cells given simultaneously with an intradermal innoculation of tumor cells, an essentially similar rejection reaction was found, although tumor cell rejection was delayed. Lymphocytes and large mononuclear cells were found in equal proportions, whereas basophilic granulocytes were always present in smaller numbers. After BCG-induced regression and in adoptively transferred immune rejection, a fibroblast component was more prominent than in untreated control tumors. This reaction tended to isolate smaller tumor cell areas into islets of decreasing sizes. In contrast with the fibroblast component of growing tumors, the proliferative pre-existing fibrous tissue in tumors undergoing regression or rejection showed a loosely arranged architecture and contained a marked cellular infiltrate. From the results of the present study it was concluded that the morphological expression of line 10 tumor rejection varies. Without immune cells, BCG is needed for the induction of a local inflammatory reaction, which was granulomatous in type and eventually led to complete tumor cell eradication.(ABSTRACT TRUNCATED AT 400 WORDS)
在同基因2系豚鼠/10号线肝细胞癌肿瘤系统中研究了免疫介导的肿瘤消退的组织学。通过在7天大的已形成肿瘤（直径8 - 10毫米）内注射活卡介苗（BCG）非特异性诱导肿瘤消退。在第7天，未治疗的10号线肿瘤存在轻度至中度炎症反应，主要由小单核细胞组成；此外还有大单核细胞和嗜碱性粒细胞。瘤内BCG治疗因小和大单核细胞及中性粒细胞的流入导致炎症反应显著增加。小单核细胞主要鉴定为淋巴细胞，而大单核细胞主要属于巨噬细胞系。瘤内给予BCG导致肉芽肿反应。观察到肿瘤细胞数量随时间减少以及炎症增加，伴有肉芽肿组织的化脓性溶解。在主动免疫和免疫脾细胞的过继转移后，动物体内发生了特异性免疫介导的肿瘤排斥。在主动免疫的动物中，肿瘤细胞迅速被排斥，从第4天起在注射部位未检测到肿瘤细胞。淋巴细胞是炎症反应的主要成分；大单核细胞存在较少，且经常观察到嗜碱性粒细胞。在用免疫脾细胞进行免疫过继转移并同时皮内接种肿瘤细胞后，发现了基本相似的排斥反应，尽管肿瘤细胞排斥延迟。淋巴细胞和大单核细胞比例相等，而嗜碱性粒细胞数量始终较少。在BCG诱导的消退和过继转移的免疫排斥后，成纤维细胞成分比未治疗的对照肿瘤中更突出。这种反应倾向于将较小的肿瘤细胞区域分隔成越来越小的岛状。与生长肿瘤的成纤维细胞成分相反，正在消退或被排斥的肿瘤中预先存在的增殖性纤维组织显示出疏松排列的结构，并含有明显的细胞浸润。从本研究结果得出结论，10号线肿瘤排斥的形态学表现各不相同。没有免疫细胞时，需要BCG来诱导局部炎症反应，该反应为肉芽肿类型并最终导致肿瘤细胞完全根除。（摘要截短至400字）
