Turcotte Simon, Rosenberg Steven A
Surgery Branch, National Cancer Institute, National Institutes of Health, 10 Center Drive, Bethesda, MD 20892, USA.
Adv Surg. 2011;45:341-60. doi: 10.1016/j.yasu.2011.04.003.
After decades of research on solid tumor immunology, immunotherapy has shown effectiveness in patients with metastatic solid cancers. Immune modulators such as IL-2 and anti-CTLA-4 can mediate tumor regression in patients with metastatic melanoma and renal cancer, two tumor types that appear exceptional in their ability to spontaneously harbor endogenous antitumor immune cells. The responses can be long lasting, but the number of patients who benefit from these molecules remains limited. Combinations of these agents with cytotoxic and biologic agents are being investigated as a means to increase response rates and in an attempt to broaden application to other cancer types. Rare responses to cancer vaccines suggest that a better understanding of the underlying biology and mechanism of actions may lead to wider application in the future. The most effective form of immunotherapy thus far, capable of eradicating large tumor burdens in melanoma patients, is the ACT of TIL given to patients after lymphodepletion. As an alternative, lymphocytes engineered to recognize tumor-associated antigens can be safely infused to patients. With this approach, tumor regression is now being reported for cancers other than melanoma, but success remains constrained by the identification of antigens expressed with high specificity by cancer cells and not by normal tissues.
经过数十年对实体瘤免疫学的研究，免疫疗法已在转移性实体癌患者中显示出有效性。诸如白细胞介素-2和抗细胞毒性T淋巴细胞相关抗原4等免疫调节剂可介导转移性黑色素瘤和肾癌患者的肿瘤消退，这两种肿瘤类型在自发容纳内源性抗肿瘤免疫细胞的能力方面显得尤为特殊。这些反应可能是持久的，但受益于这些分子的患者数量仍然有限。正在研究将这些药物与细胞毒性药物和生物制剂联合使用，以提高反应率，并试图将其应用范围扩大到其他癌症类型。对癌症疫苗的罕见反应表明，更好地理解其潜在生物学特性和作用机制可能会在未来带来更广泛的应用。迄今为止，最有效的免疫疗法形式是在淋巴细胞清除后将肿瘤浸润淋巴细胞输给黑色素瘤患者，这种疗法能够消除大量肿瘤负荷。作为一种替代方法，可以将经过工程改造以识别肿瘤相关抗原的淋巴细胞安全地输注给患者。通过这种方法，现在已有除黑色素瘤之外的其他癌症出现肿瘤消退的报道，但成功仍然受到癌细胞而非正常组织高特异性表达的抗原识别的限制。
