MHC antigen expression by melanomas recovered from mice treated with allogeneic mouse fibroblasts genetically modified for interleukin-2 secretion and the expression of melanoma-associated antigens.
MHC antigen expression by melanomas recovered from mice treated with allogeneic mouse fibroblasts genetically modified for interleukin-2 secretion and the expression of melanoma-associated antigens.
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黑色素瘤的 MHC 抗原表达是从用同种异体小鼠成纤维细胞处理的小鼠中恢复的，该小鼠成纤维细胞经过基因改造，可分泌白细胞介素 2 并表达黑色素瘤相关抗原。
DOI：
10.1007/bf01525640
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发表时间：
1994
期刊：
影响因子：
--
通讯作者：
Cohen,EP
中科院分区：
文献类型：
--
作者：
Kim,TS;Cohen,EP
最近肿瘤疾病的免疫治疗方法包括将白细胞介素-2 （IL-2）表达能力基因引入自体恶性细胞。用il -2分泌细胞治疗荷瘤实验动物成功地诱导部分缓解，有时完全缓解。然而，在大多数情况下，尽管延迟，肿瘤仍在继续发展。本文描述了在分泌il -2、黑色素瘤抗原阳性细胞免疫原（RLBA-IL-2细胞）治疗的C57BL/6小鼠（H-2b）中持续存在的B16黑色素瘤（H-2b）的某些特征。与第一次注射的黑色素瘤细胞不同，用RLBA-IL-2细胞处理的小鼠恢复的B16细胞缺乏MHC I类决定因子的表达，但不缺乏II类决定因子。MHC I类表达缺陷与RLBA-IL-2细胞免疫小鼠脾脏细胞毒性T淋巴细胞（CTL）的抵抗相关。在非il -2分泌、黑色素瘤抗原阳性细胞构建体（RLBA-ZipNeo细胞）处理的小鼠中，黑色素瘤也缺乏MHC I类决定因子的表达，并且黑色素瘤细胞对RLBA-ZipNeo细胞免疫的小鼠的CTL具有抗性。因此，黑色素瘤相关抗原的表达而非il -2分泌与持续性黑色素瘤中MHC I类表达缺陷相关。在分泌il -2、黑色素瘤抗原阴性的LM细胞（LM- il -2）处理的小鼠中，持续存在的黑色素瘤表达MHC I类抗原证实了这一点；这与未经治疗的小鼠的黑色素瘤相同。干扰素γ (IFNγ)或n-甲基-n′-硝基-n -亚硝基胍（MNNG）对抗黑色素瘤CTL敏感性的影响表明，MHC I类抗原参与了黑色素瘤阳性免疫原处理小鼠持久黑色素瘤细胞的免疫抵抗。用IFNγ或MNNG治疗耐药黑素瘤刺激MHC I类抗原表达，并恢复了il -2分泌或非分泌黑素瘤抗原阳性细胞免疫原免疫小鼠的细胞对CTL的敏感性。预先用MHC I类决定因子抗体处理处理的细胞抑制了细胞对RLBA-IL-2细胞免疫小鼠CTL的敏感性。
Recent approaches toward the immunotherapy of neoplastic disease involve the introduction of expression-competent genes for interleukin-2 (IL-2) into autologous malignant cells. Treatment of tumor-bearing experimental animals with the IL-2-secreting cells successfully induces partial and at times complete remissions. In most instances, however, although delayed, progressive tumor growth continues. Here, certain of the characteristic of B16 melanomas (H-2b) persisting in C57BL/6 mice (H-2b) treated with an IL-2-secreting, melanoma-antigen-positive cellular immunogen (RLBA-IL-2 cells) are described. Unlike the melanoma cells first injected, B16 cells recovered from mice treated with RLBA-IL-2 cells were deficient in the experssion of MHC class I, but not class II determinants. Deficient MHC class I expression correlated with the cells' resistance to cytotoxic T lymphocytes (CTL) from the spleens of mice immunized with RLBA-IL-2 cells. Melanomas persisting in mice treated with non-IL-2-secreting, melanoma-antigen-positive cell constructs (RLBA-ZipNeo cells) were also deficient in the expression of MHC class I determinants, and the melanoma cells were resistant to CTL from mice immunized with RLBA-ZipNeo cells. Thus, the expression of melanoma-associated antigens rather than IL-2-secretion correlated with deficient MHC class I expression by the persistent melanomas. This point was substantiated by the expression of MHC class I antigens by melanomas persisting in mice treated with IL-2-secreting, melanoma-antigen-negative LM cells (LM-IL-2); it was equivalent to that of melanomas in untreated mice. The involvement of MHC class I antigens in the immune resistance of persistent melanoma cells from mice treated with the melanoma-autigen-positive immunogens was indicated by the effect of interferon γ (IFNγ) orN-methyl-N′-nitro-N-nitrosoguanidine (MNNG) on the susceptibility of the cells to anti-melanoma CTL. Treatment of the resistant melanomas with IFNγ or MNNG stimulated MHC class I antigen expression and restored the cells' sensitivity to CTL from mice immunized with IL-2-secreting or nonsecreting, melanoma-antigen-positive cellular immunogens. Prior treatment of the treated cells with antibodies to MHC class I determinants inhibited the cells' susceptibility to CTL from mice immunized with RLBA-IL-2 cells.