Pimm M V, Hopper D G, Baldwin R W
Dev Biol Stand. 1977;38:349-54.
BCG (Glaxo) and C. parvum (Wellcome CN 6134) have been examined for suppression of growth of a range of syngeneically transplanted rat tumours, both carcinogen-induced and of spontaneous origin. Treatment by locally applied adjuvant controlled growth of both immunogenic and non-immunogenic tumours, and the response to highly immunogenic tumours was not abolished by host immunosuppression with whole body irradiation known to abrogate induction of tumour-specific immunity. In addition, rat tumour xenografts in congenitally athymic mice were suppressed by admixture with BCG or C. parvum. In contrast to these findings in immunoincompetent animals, host phagocytic cell depletion, by systemic administration of silica, a known macrophage poison, abrogated adjuvant contact suppression of tumours in syngeneic rats and athymic mice. These findings suggest that tumour suppression by regionally applied adjuvants may be more dependent upon local activation of host macrophages than upon generalized stimulation of lymphocyte mediated responses. This is further supported by the market correlation, within a range of tumours, between susceptibility to regionally applied BCG and normal levels of host macrophage infiltration, and in addition the facilitation of tumour suppression achieved by macrophage enrichment of tumour cell: BCG inocula.
已对卡介苗(葛兰素史克公司生产)和微小隐孢子虫(威康公司CN 6134)进行了检测,以观察它们对一系列同基因移植大鼠肿瘤生长的抑制作用,这些肿瘤既有致癌物诱发的,也有自发产生的。局部应用佐剂治疗可控制免疫原性和非免疫原性肿瘤的生长,并且已知全身照射可消除肿瘤特异性免疫诱导,从而使宿主免疫抑制,但高度免疫原性肿瘤对其的反应并未消除。此外,先天性无胸腺小鼠体内的大鼠肿瘤异种移植物通过与卡介苗或微小隐孢子虫混合而受到抑制。与这些在免疫功能不全动物中的发现形成对比的是,通过全身给予二氧化硅(一种已知的巨噬细胞毒素)使宿主吞噬细胞耗竭,可消除同基因大鼠和无胸腺小鼠中佐剂对肿瘤的接触抑制作用。这些发现表明,局部应用佐剂对肿瘤的抑制作用可能更多地依赖于宿主巨噬细胞的局部激活,而不是淋巴细胞介导反应的全身性刺激。一系列肿瘤中对局部应用卡介苗的敏感性与宿主巨噬细胞浸润的正常水平之间的相关性,以及通过肿瘤细胞与卡介苗接种物的巨噬细胞富集实现的肿瘤抑制促进作用,进一步支持了这一点。