Zöller M
Institute of Nuclear Medicine, German Cancer Research Center, Heidelberg.
Clin Exp Metastasis. 1988 Sep-Oct;6(5):411-29. doi: 10.1007/BF01760576.
Treatment of tumor cells with interferon-gamma (IFN) frequently reduces their susceptibility towards NK cells and results in augmented expression of MHC antigens, which may increase immunogenicity of tumor cells. Depending on the relative strength of these opposing effects, i.e. escape from non-adaptive immune defense versus facilitated activation of T-cell-mediated defense, IFN-treatment may be beneficial or disadvantageous for the tumor-bearing host. This is demonstrated for the variants F1 and F10 of the B16 melanoma, which differ in metastasizing capacity. IFN-treatment of B16-F1 melanoma cells significantly reduced susceptibility towards non-adaptive immune defense, and increased metastasizing potential. On the other hand, H2K antigen expression was augmented by a factor of 50; concomitantly, lysability by CTL was increased, together with the number and expansion rate of cytotoxic T-cell precursors (CTLp) recruited after immunization with IFN-treated B16-F1. The benefit of increased antigenicity and immunogenicity outweighed the disadvantage or reduced susceptibility towards non-adaptive immune defense. B16-F10 cells were less susceptible to NK cells, expression of MHC antigens was found to be stronger and they were more immunogenic than B16-F1 cells. After IFN-treatment, susceptibility to non-adaptive immune defense was further reduced. Expression of MHC antigens as well as antigenicity and immunogenicity were only moderately augmented. As a consequence, the decreased susceptibility to non-adaptive immune defense was dominating in the tumor bearing host and could not be counterbalanced by immunization with IFN-treated B16-F10 cells. We interpret these data to show that a precise knowledge of the relative decrease in susceptibility to non-adaptive immune defense, the relative increase in MHC antigen expression, antigenicity and immunogenicity may allow a more precise prognosis of the influence of IFN on metastatic capacity in the B16 system, and eventually also in a clinical therapeutic regimen.
用γ干扰素（IFN）处理肿瘤细胞常常会降低它们对自然杀伤细胞（NK细胞）的敏感性，并导致主要组织相容性复合体（MHC）抗原表达增加，这可能会增强肿瘤细胞的免疫原性。根据这些相反作用的相对强度，即逃避非适应性免疫防御与促进T细胞介导的防御激活，IFN处理对荷瘤宿主可能有益也可能有害。这在B16黑色素瘤的F1和F10变体中得到了证明，它们在转移能力上有所不同。用IFN处理B16 - F1黑色素瘤细胞显著降低了其对非适应性免疫防御的敏感性，并增加了转移潜能。另一方面，H2K抗原表达增加了50倍；与此同时，细胞毒性T淋巴细胞（CTL）的可裂解性增加，在用经IFN处理的B16 - F1免疫后募集的细胞毒性T细胞前体（CTLp）的数量和扩增率也增加。抗原性和免疫原性增加带来的益处超过了对非适应性免疫防御敏感性降低的不利之处。B16 - F10细胞对NK细胞的敏感性较低，发现其MHC抗原表达更强，并且比B16 - F1细胞更具免疫原性。经IFN处理后，对非适应性免疫防御的敏感性进一步降低。MHC抗原的表达以及抗原性和免疫原性仅适度增加。因此，在荷瘤宿主中，对非适应性免疫防御敏感性的降低占主导地位，并且不能通过用经IFN处理的B16 - F10细胞免疫来抵消。我们解释这些数据表明，精确了解对非适应性免疫防御敏感性的相对降低、MHC抗原表达、抗原性和免疫原性的相对增加，可能有助于更精确地预测IFN对B16系统转移能力的影响，最终也有助于预测其在临床治疗方案中的影响。
