Forni G, Fujiwara H, Martino F, Hamaoka T, Jemma C, Caretto P, Giovarelli M
Institute of Microbiology, University of Torino, Italy.
Cancer Metastasis Rev. 1988 Dec;7(4):289-309. doi: 10.1007/BF00051371.
Two main kinds of immune strategy are possible against neoplasia. The first potentiates a selected effector arm. In vitro culture with exogenous interleukin-2 (IL-2) increases the activity of natural killer cells and leads to the expansion of T cytotoxic lymphocytes. Systemic reinfusion of both of these cells with high doses of IL-2 mediates the regression of a variety of murine and human tumors. In an alternative strategy, a few regulatory lymphocytes turn on immune reactivity by triggering a cascade of interconnected effector functions. The efficacy of this strategy rests on the repertoire of effector mechanisms moved to action. An effective immunoregulatory maneuver is the addition of helper determinants on the surface of tumor cells. Its power can be further increased by the pre-induction of helper T lymphocytes specific to the helper determinants. This approach can be achieved in mice by coupling muramyl dipeptides to tumor cells, along with eliciting T lymphocytes specifically reactive to Bacillus Calmette-Guerin. Noncytotoxic T helper lymphocytes produce factors which recruit nonspecific (macrophages) as well as specific (cytolytic T lymphocytes) anti-tumor attacking cells. In this way protection can be afforded against primary tumors and metastases, as well as leukemia cells. As the activity of helper lymphocytes rests mostly on lymphokine release, the use of molecularly defined lymphokines mimicking T-helper functions has also been attempted. In a few experimental models, the association of low doses of IL-2 with non-reactive lymphocytes from tumor-bearing mice promotes an effective anti-tumor reaction in the host. Moreover, the combination of distinct lymphokines can also build a molecularly defined helper system able to activate in sequence non-specific and specific anti-tumor reactions in vivo. Trials intended to evaluate the clinical impact of these helper approaches in the management of human tumors are being started or are already under way.
针对肿瘤形成可能存在两种主要的免疫策略。第一种是增强选定的效应器分支。用外源性白细胞介素-2（IL-2）进行体外培养可增强自然杀伤细胞的活性，并导致细胞毒性T淋巴细胞的扩增。将这两种细胞与高剂量的IL-2进行全身再输注可介导多种鼠类和人类肿瘤的消退。在另一种策略中，一些调节性淋巴细胞通过触发一系列相互关联的效应功能来开启免疫反应性。这种策略的有效性取决于被激活的效应机制的全部组成。一种有效的免疫调节手段是在肿瘤细胞表面添加辅助决定簇。通过预先诱导对辅助决定簇具有特异性的辅助性T淋巴细胞，其作用可以进一步增强。在小鼠中，可以通过将胞壁酰二肽与肿瘤细胞偶联，同时引发对卡介苗具有特异性反应的T淋巴细胞来实现这种方法。无细胞毒性的辅助性T淋巴细胞产生的因子可募集非特异性（巨噬细胞）以及特异性（溶细胞性T淋巴细胞）抗肿瘤攻击细胞。通过这种方式，可以对原发性肿瘤、转移瘤以及白血病细胞提供保护。由于辅助性淋巴细胞的活性主要依赖于淋巴因子的释放，因此也尝试使用模拟T辅助功能的分子定义的淋巴因子。在一些实验模型中，低剂量的IL-2与荷瘤小鼠的无反应性淋巴细胞联合使用可促进宿主产生有效的抗肿瘤反应。此外，不同淋巴因子的组合还可以构建一个分子定义的辅助系统，能够在体内依次激活非特异性和特异性抗肿瘤反应。旨在评估这些辅助方法在人类肿瘤治疗中的临床影响的试验正在启动或已经在进行中。
