Lieberman R, Wybran J, Epstein W
Cancer. 1975 Mar;35(3):756-77. doi: 10.1002/1097-0142(197503)35:3<756::aid-cncr2820350331>3.0.co;2-z.
Six patients with intradermal metastases of malignant melanoma were treated with intralesional bacile Calmette-Guérin (BCG). Four patients showed a good response with regression of injected, and in some cases, uninjected lesions, whereas two developed metastatic viscereal disease and died. Three of the six patients had complete regression of all lesions, and one exhibited complete regression of untreated lesions. All remain free of disease. The fourth patient had complete regression of injected and of some untreated lesions, but developed widespread dissemination and died. Preliminary experiments suggest the presence of a blocking factor in his sera which abrogates the lymphocyte stimulation in response to melanoma antigens. Three of four responders (i.e. those patients in whom treated lesions decreased in size by more than 50% for more than 1 month) showed a dramatic increase in lymphocyte stimulation to melanoma antigens. All responders (four out of four) had a marked increase to phytohemagglutinin (PHA), whereas non responders had no increase in lymphocyte stimulation either to melanoma antigens or PHA. Two of four responders showed inhibition of leukocyte migration to melanoma antigens before BCG, and two of four responders were positive after BCG. Of the nonresponders, one was positive and one negative before BCG; this remained the same after. There was a marked increase in active rosette forming cells in all responders and in one of the two nonresponders. Histopathologic studies at 3 hours, 6 hours, 24 hours, 14 days, and 4 weeks after BCG showed a definite sequence of events occurred, progressing from 1) inflammatory cell response at the periphery of the lesion, disruption of melanogenesis, extensive dumping of pigment from melanoma cells, proceeding to actual cell death at 24 hours, to 2) macrophages containing melanin and granulomas replacing tumor by 2 weeks. These studies suggest that BCG activates both specific and nonspecific immune responses. Thus, in vitro parameters of cellular immunity, including migration inhibitory factor production and inhibition of leukocyte migration, are affected by intralesional BCG, and some, particularly the lymphocyte stimulation and rosette test, seem to correlate with the clinical response of the patients.
6例恶性黑色素瘤皮内转移患者接受了病灶内注射卡介苗（BCG）治疗。4例患者反应良好，注射病灶及部分未注射病灶消退，而2例发生内脏转移并死亡。6例患者中有3例所有病灶完全消退，1例未治疗病灶完全消退。所有患者均无疾病复发。第4例患者注射病灶及部分未治疗病灶完全消退，但出现广泛播散并死亡。初步实验表明其血清中存在一种阻断因子，可消除淋巴细胞对黑色素瘤抗原的刺激反应。4例有反应者（即治疗病灶大小缩小超过50%且持续超过1个月的患者）中有3例对黑色素瘤抗原的淋巴细胞刺激反应显著增强。所有有反应者（4例中有4例）对植物血凝素（PHA）的反应均显著增强，而无反应者对黑色素瘤抗原或PHA的淋巴细胞刺激反应均未增强。4例有反应者中有2例在BCG治疗前对黑色素瘤抗原的白细胞迁移有抑制作用，4例中有2例在BCG治疗后呈阳性。在无反应者中，1例在BCG治疗前呈阳性，1例呈阴性；治疗后情况相同。所有有反应者及2例无反应者中的1例活性玫瑰花结形成细胞显著增加。在BCG治疗后3小时、6小时、24小时、14天和4周进行的组织病理学研究显示，出现了明确的事件序列，从1）病灶周边的炎症细胞反应、黑色素生成中断、黑色素瘤细胞大量色素释放，到24小时时实际细胞死亡，发展为2）2周时含黑色素的巨噬细胞和肉芽肿取代肿瘤。这些研究表明BCG可激活特异性和非特异性免疫反应。因此，病灶内注射BCG会影响细胞免疫的体外参数，包括迁移抑制因子产生和白细胞迁移抑制，其中一些参数，特别是淋巴细胞刺激和玫瑰花结试验，似乎与患者的临床反应相关。
