Botti C, Seregni E, Ferrari L, Martinetti A, Bombardieri E
Nuclear Medicine Department, Istituto Nazionale per lo Studio e la Cura dei Tumori, Milano, Italy.
Int J Biol Markers. 1998 Apr-Jun;13(2):51-69. doi: 10.1177/172460089801300201.
The concept of the immunological surveillance against neoplastic cells was initially proposed by Erlich in 1909 and later elaborated by Burnet. This hypothesis states that the normal function of the immune system, in particular the cell-mediated immunity, is to recognize and destroy the transformed and proliferating tumor cells. The role of cell-mediated immunity during the first steps of tumorigenesis remains controversial. However, there is certain evidence about its importance in the progression and dissemination of cancer. The frequent immunosuppressed condition of cancer patients at tumor relapse or recurrence of secondary tumors is a clinical sign supporting this hypothesis, and many studies have demonstrated a defective immune response in patients diagnosed with advanced cancer. Several mechanisms of escape from the immune surveillance have been described, including the immunoselection of tumor antigen-negative variants, the downregulation of MHC class I expression, suppressive T cells, and the elaboration of immunosuppressive cytokines and other factors. Because of the technical difficulty of isolating the very small amounts from culture supernatants or body fluids, only a few of these substances have been characterized and studied with respect to their biological activity: transforming growth factor-beta (TGF-beta), the protein p15E, interleukin 10 (IL-10), prostaglandin E2 (PGE2), mucins, suppressive E-receptor (SER), immunosuppressive acidic protein (IAP), and adhesion molecules. The possibility of monitoring cancer patients by testing biochemical factors related to cancer growth led to a proposal to measure a number of these factors as tumor markers. Some of them, e.g. mucins, enjoy the consensus of the oncologic community, as for some indications they can help the clinician in the management of cancer patients. Except for the class of mucins, the other above-mentioned immunosuppressive factors have not found any clinical application in the laboratory routine because the information deriving from their measurement, although of speculative and scientific interest, has limited clinical value at present. Nevertheless, even if they have no impact on patient management, these substances do have a potential role to play in the study of cancer patients, and should be taken into account when developing new therapeutic strategies.
针对肿瘤细胞的免疫监视概念最初由埃尔利希于1909年提出，后来由伯内特进一步阐述。该假说指出，免疫系统的正常功能，特别是细胞介导的免疫，是识别并摧毁转化和增殖的肿瘤细胞。细胞介导的免疫在肿瘤发生第一步中的作用仍存在争议。然而，有一定证据表明其在癌症进展和扩散中具有重要性。癌症患者在肿瘤复发或出现继发性肿瘤时频繁出现免疫抑制状态，这是支持该假说的一个临床迹象，许多研究已证明晚期癌症患者存在免疫反应缺陷。已经描述了几种逃避免疫监视的机制，包括肿瘤抗原阴性变体的免疫选择、MHC I类表达的下调、抑制性T细胞以及免疫抑制细胞因子和其他因子的产生。由于从培养上清液或体液中分离出极少量物质存在技术困难，这些物质中只有少数已根据其生物活性进行了表征和研究：转化生长因子-β（TGF-β）、蛋白质p15E、白细胞介素10（IL-10）、前列腺素E2（PGE2）、粘蛋白、抑制性E受体（SER）、免疫抑制酸性蛋白（IAP）和粘附分子。通过检测与癌症生长相关的生化因子来监测癌症患者的可能性，促使人们提出将其中一些因子作为肿瘤标志物进行测量。其中一些，例如粘蛋白，得到了肿瘤学界的共识，因为在某些情况下它们可以帮助临床医生管理癌症患者。除了粘蛋白类别外，上述其他免疫抑制因子在实验室常规检查中尚未发现任何临床应用，因为从其测量中获得的信息虽然具有推测性和科学价值，但目前临床价值有限。然而，即使它们对患者管理没有影响，这些物质在癌症患者的研究中确实具有潜在作用，并且在制定新的治疗策略时应予以考虑。
