Lattime E C, Stutman O
Immunology Program, Memorial Sloan-Kettering Cancer Center, New York 10021.
J Immunol. 1989 Dec 15;143(12):4317-23.
The relationship between in vivo tumor growth and resistance to TNF in WEHI-164 cells has been examined. When a highly TNF-sensitive clone of WEHI-164 was grown in vivo in syngeneic mice it became resistant to rTNF such that a 4 to 5 log higher concentration of TNF was required to produce tumor lysis in vitro. When compared with an in vitro selected TNF-resistant variant, the in vivo selected line was significantly more tumorigenic. The resistant phenotype of both the in vivo and in vitro selected variants was stable in culture and both selected lines were also resistant to lysis by syngeneic spleen cells with natural cytotoxic activity. The parental clone and the two variants were equally sensitive to lysis by allo-CTL and expressed similar levels of MHC class I Ag. Resistance to TNF in the two variants was not a function of de novo production of TNF measured as supernatant TNF activity or TNF mRNA expression. These studies are the first to demonstrate that in vivo tumor growth results in resistance to TNF and therefore may have direct relevance to the efficacy of TNF in the treatment of human neoplasms.
已经研究了WEHI-164细胞体内肿瘤生长与对TNF抗性之间的关系。当一个对TNF高度敏感的WEHI-164克隆在同基因小鼠体内生长时，它对rTNF产生了抗性，以至于在体外需要4到5个对数更高浓度的TNF才能产生肿瘤溶解。与体外选择的TNF抗性变体相比，体内选择的细胞系具有明显更高的致瘤性。体内和体外选择的变体的抗性表型在培养中是稳定的，并且两个选择的细胞系也对具有天然细胞毒性活性的同基因脾细胞的裂解具有抗性。亲本克隆和两个变体对同种异体CTL的裂解同样敏感，并表达相似水平的MHC I类抗原。两个变体中对TNF的抗性不是以上清液TNF活性或TNF mRNA表达来衡量的TNF从头产生的作用。这些研究首次证明体内肿瘤生长导致对TNF的抗性，因此可能与TNF治疗人类肿瘤的疗效直接相关。
