Sakita I, Monden T, Nagaoka H, Katsumoto Y, Wakasugi T, Tomita N, Takeda T, Kobayashi T, Shimano T, Mori T
Department of Surgery II, Osaka University Medical School, Japan.
Biotherapy. 1993;6(2):103-12. doi: 10.1007/BF01877423.
We have previously reported that the antitumor effect of OK-432, a streptococcal preparation, is markedly augmented when injected intratumorally together with fibrinogen (OK-432/fbg) [1]. In order to elucidate the effects of this immunotherapy on regional lymph nodes (RLN), we carried out both morphological and functional analyses of the RLN from colonic cancer patients treated with OK-432/fbg. Computer-aided morphometry revealed that the maximal cross-sectional areas and the broadest diameters of the RLN were significantly greater (p < 0.01) in patients who had undergone local immunotherapy than in patients who had not. The component structures of RLN, such as sinus, follicle and paracortex, were all enlarged in the OK-432/fbg-treated patients, and necrosis of metastatic tumors was observed. RLN lymphocytes recovered from OK-432/fbg treated patients showed elevated reactivity to phytohemagglutinin (PHA) and the stimulation index was clearly higher than that of control patients. Flow cytometric analysis revealed a predominance of T-cells, especially CD4 subsets, and higher positivity for both CD25 and HLA-DR. Furthermore, RLN lymphocytes killed more effectively K562 and Daudi cells in the patients who had had immunotherapy. These results suggest that the effect of local immunotherapy with OK-432/fbg is not restricted to the site of injection but extends to the lymph nodes, and contributes to tumor regression through the augmentation of cellular immunity.
我们之前曾报道，链球菌制剂OK-432与纤维蛋白原联合瘤内注射（OK-432/fbg）时，其抗肿瘤作用会显著增强[1]。为了阐明这种免疫疗法对区域淋巴结（RLN）的影响，我们对接受OK-432/fbg治疗的结肠癌患者的RLN进行了形态学和功能分析。计算机辅助形态测量显示，接受局部免疫治疗的患者的RLN最大横截面积和最宽直径显著大于未接受治疗的患者（p < 0.01）。在接受OK-432/fbg治疗的患者中，RLN的组成结构，如窦、滤泡和副皮质均增大，且观察到转移瘤坏死。从接受OK-432/fbg治疗的患者中回收的RLN淋巴细胞对植物血凝素（PHA）的反应性升高，刺激指数明显高于对照患者。流式细胞术分析显示T细胞占优势，尤其是CD4亚群，且CD25和HLA-DR的阳性率更高。此外，接受免疫治疗患者的RLN淋巴细胞对K562和Daudi细胞的杀伤更有效。这些结果表明，OK-432/fbg局部免疫治疗的效果不仅局限于注射部位，还扩展至淋巴结，并通过增强细胞免疫促进肿瘤消退。
