Rosenberg S A
Surgery Branch, National Cancer Institute, National Institutes of Health, Bethesda, Maryland 20892, USA.
Cancer J Sci Am. 1995 Jul-Aug;1(2):90-100.
Knowledge of the nature of immune reactivity to human tumors has increased dramatically in the past decade. Prior to this, there was significant doubt as to whether tumor antigens actually existed on growing human cancers, and if so, there was considerable skepticism about whether immunotherapies could ever be used to affect growing tumors. The development of reproducible techniques for generating human lymphocytes with reactivity against tumor antigens, the demonstration that the recognition of tumor antigens obeys the same immunologic laws of MHC restriction that characterize immunologic reactions against other antigens, and the demonstration that T-cell transfer therapies--as well as immunotherapies using immune stimulants such as IL-2--could cause the regression of established growing cancers in humans have transformed the study of human tumor immunology from a speculative science to one with concrete applications to the treatment of patients with cancer. The cloning of the genes encoding cancer antigens and the molecular identification of the encoded proteins has opened new possibilities for the development of cancer treatments. Although several human cancer antigens have been identified, only a small number of histologic types of tumors have been studied and these investigations need to be extended to identify putative tumor antigens expressed on common epithelial neoplasms. There is considerable uncertainty surrounding the mechanism by which immune reactions to these cancer antigens are generated in humans. Thus far, all of the cancer rejection antigens recognized by TIL, as well as additional antigens described by others, represent antigens that are encoded by normal nonmutated genes that are expressed on selected normal tissues as well as on tumors. An understanding of the mechanisms by which the tumor can break tolerance to these normal antigens represents a significant challenge to immunologic studies, the answer to which may provide additional insight into methods for enhancing antitumor immune responses.
在过去十年中，人们对人类肿瘤免疫反应本质的认识有了显著提高。在此之前，对于正在生长的人类癌症上是否真的存在肿瘤抗原存在重大疑问，而且即便存在，对于免疫疗法是否能够用于影响正在生长的肿瘤也存在相当多的怀疑。能够产生针对肿瘤抗原具有反应性的人类淋巴细胞的可重复技术的发展，肿瘤抗原的识别遵循与针对其他抗原的免疫反应相同的MHC限制免疫法则的证明，以及T细胞转移疗法——以及使用如白细胞介素-2等免疫刺激剂的免疫疗法——能够使人类已确立生长的癌症消退这些事实，已经将人类肿瘤免疫学研究从一门推测性科学转变为一门有具体应用于癌症患者治疗的科学。编码癌症抗原的基因的克隆以及所编码蛋白质的分子鉴定为癌症治疗的发展开辟了新的可能性。尽管已经鉴定出几种人类癌症抗原，但仅研究了少数组织学类型的肿瘤，这些研究需要扩展以鉴定在常见上皮性肿瘤上表达的假定肿瘤抗原。关于人类中针对这些癌症抗原产生免疫反应的机制存在相当大的不确定性。到目前为止，肿瘤浸润淋巴细胞所识别的所有癌症排斥抗原，以及其他人描述的其他抗原，都代表由正常非突变基因编码的抗原，这些基因在选定的正常组织以及肿瘤上表达。理解肿瘤能够打破对这些正常抗原的耐受性的机制对免疫学研究构成了重大挑战，其答案可能会为增强抗肿瘤免疫反应的方法提供更多见解。
