Hadden J W
University of South Florida College of Medicine, Department of Internal Medicine, Tampa, USA.
Int J Immunopharmacol. 1999 Feb;21(2):79-101. doi: 10.1016/s0192-0561(98)00077-0.
Adenocarcinomas of the breast behave clinically and epidemiologically in ways that show host resistance factors are important for outcome in addition to grade and stage of malignancy. Immune reactivity to autologous tumors is indicated by the general presence of lymphoid infiltration (LI) and regional lymph node changes; however, these changes predict favorable outcome only in non-metastatic disease. LI is characterized by CD4+ and CD8+ tumor infiltrating lymphocytes reflecting latent cell-mediated immunity (CMI). CMI and humoral immune reactivity have been demonstrated to autologous tumor and a variety of tumor-associated antigens (TAA) have been implicated including CEA, HER-2/neu, MAGE-1, p53, T/Tn and MUC-1. Immune incompetence involving CMI is progressive with the stage of breast cancer and is prognostically significant. Immunotherapy of several types has been designed to address this immunodeficiency and the TAAs involved. Animal models have employed drug therapy, cytokine transfection, vaccines with autologous tumor, cytokines like interferon alpha (IFN-alpha) and interleukin-2 (IL-2), TAA tumor vaccines, and immunotoxins with evidence of tumor regression by immunologic means. Immunotherapy of human breast cancer is a rapidly growing experimental area. Positive results have been obtained with natural IFN and interleukins, particularly in combination strategies (but not with high dose recombinant IFN or IL-2), with autologous tumor vaccine (but not yet with transfected autologous tumor); with a mucin carbohydrate vaccine (Theratope) in a combination strategy (but not with mucin core antigen) and with several immunotoxins. Combination strategies involving immunorestoration, contrasuppression, adjuvant, and immunotoxins are suggested for the future.
乳腺癌的腺癌在临床和流行病学方面的表现表明，除了恶性肿瘤的分级和分期外，宿主抵抗因素对预后也很重要。淋巴样浸润（LI）和区域淋巴结变化的普遍存在表明对自体肿瘤有免疫反应性；然而，这些变化仅在非转移性疾病中预示着良好的预后。LI的特征是CD4+和CD8+肿瘤浸润淋巴细胞，反映潜在的细胞介导免疫（CMI）。已证明对自体肿瘤有CMI和体液免疫反应性，并且涉及多种肿瘤相关抗原（TAA），包括癌胚抗原（CEA）、人表皮生长因子受体2/neu（HER-2/neu）、黑色素瘤相关抗原1（MAGE-1）、p53、T/Tn和粘蛋白1（MUC-1）。涉及CMI的免疫无能随着乳腺癌的分期而进展，并且在预后方面具有重要意义。已经设计了几种类型的免疫疗法来解决这种免疫缺陷以及所涉及的TAA。动物模型采用了药物治疗、细胞因子转染、自体肿瘤疫苗、细胞因子如干扰素α（IFN-α）和白细胞介素-2（IL-2）、TAA肿瘤疫苗以及免疫毒素，有通过免疫手段使肿瘤消退的证据。人乳腺癌的免疫疗法是一个快速发展的实验领域。天然干扰素和白细胞介素已取得阳性结果，特别是在联合策略中（但高剂量重组干扰素或IL-2不行）、自体肿瘤疫苗（但转染的自体肿瘤尚未成功）、联合策略中的粘蛋白碳水化合物疫苗（Theratope）（但粘蛋白核心抗原不行）以及几种免疫毒素。未来建议采用涉及免疫恢复、反抑制、佐剂和免疫毒素的联合策略。
