Evans R, Duffy T M, Shultz L D
Jackson Laboratory, Bar Harbor, Maine 04609.
Cancer Immunol Immunother. 1988;26(1):35-42. doi: 10.1007/BF00199845.
Adoptive immunotherapy, consisting of cyclophosphamide injection and the i.v. transfer of tumor-sensitized T cells, resulted in rejection of the immunogenic fibrosarcoma, MCA/76-9, by syngeneic C57BL/6J (B6) mice. The same treatment of tumor-bearing congenic immunodeficient mice, homozygous for the deleterious mutations nude (nu) and rhino (hrrh), did not result in tumor rejection. Paradoxically, the intratumor and intrasplenic changes taking place in each of the three strains after therapy were indistinguishable. There was an increase in Thy-1+, Ly-2+, or L3T4+ cells at the tumor site 8 days after adoptive immunotherapy and a similar increase in Thy-1+ cells in the spleen. Moreover, the T cells isolated from the tumors or spleens from each genotype were shown to be specifically cytotoxic in vitro as well as in an in vivo Winn assay. Further evidence that immune amplification had occurred in the immunological mutant mice was provided by experiments showing (a) the ability of spleen cells from tumor-bearers and those tested after therapy to produce IL-2 in response to Con A stimulation and (b) an increase in class II-MHC antigen expression by tumor-associated macrophages. The data suggest that, although amplification of antitumor immune responses occurred in the immunological mutants, the absence of a critical host factor limited the potency of the antitumor response.
过继性免疫疗法，包括注射环磷酰胺以及静脉注射肿瘤致敏T细胞，可使同基因C57BL/6J（B6）小鼠排斥免疫原性纤维肉瘤MCA/76 - 9。对荷瘤的同基因免疫缺陷小鼠（纯合有有害突变裸鼠（nu）和犀牛鼠（hrrh））进行相同治疗，并未导致肿瘤排斥。矛盾的是，治疗后三种品系小鼠各自肿瘤内和脾脏内发生的变化并无差异。过继性免疫疗法8天后，肿瘤部位Thy - 1 +、Ly - 2 +或L3T4 +细胞增加，脾脏中Thy - 1 +细胞也有类似增加。此外，从每种基因型的肿瘤或脾脏中分离出的T细胞在体外以及体内温氏试验中均显示具有特异性细胞毒性。实验表明（a）荷瘤小鼠和治疗后检测的小鼠脾脏细胞在受到刀豆蛋白A刺激时产生白细胞介素-2的能力，以及（b）肿瘤相关巨噬细胞II类主要组织相容性复合体抗原表达增加，为免疫缺陷小鼠中发生免疫放大提供了进一步证据。数据表明，尽管免疫缺陷小鼠中发生了抗肿瘤免疫反应的放大，但关键宿主因子的缺失限制了抗肿瘤反应的效力。
