Smyth M J, Thia K Y, Cretney E, Kelly J M, Snook M B, Forbes C A, Scalzo A A
Cellular Immunity Laboratory, Austin Research Institute, Heidelberg, Victoria, Australia.
J Immunol. 1999 Jun 1;162(11):6658-62.
We provide the first demonstration, using experimental and spontaneous models of metastasis in C57BL/6 (B6) (RM-1 prostate carcinoma) and BALB/c (DA3 mammary carcinoma) mice, that tumor metastasis is primarily controlled by perforin-dependent cytotoxicity mediated by NK1.1+ cells. MHC class Ilow RM-1 and DA3 tumor cells were sensitive in vitro to Fas-mediated lysis or spleen NK cells in a perforin-dependent fashion. Perforin-deficient NK cells did not lyse these tumors, and perforin-deficient mice were 10-100-fold less proficient than wild-type mice in rejecting the metastasis of tumor cells to the lung. Fas ligand mutant gld mice displayed uncompromised protection against tumor metastasis. Depletion of NK subsets resulted in greater numbers of metastases than observed in perforin-deficient mice, suggesting that perforin-independent effector functions of NK cells may also contribute to protection from tumor metastasis.
我们利用C57BL/6（B6）（RM-1前列腺癌）和BALB/c（DA3乳腺癌）小鼠的转移实验模型和自发模型首次证明，肿瘤转移主要由NK1.1+细胞介导的穿孔素依赖性细胞毒性控制。MHC II低表达的RM-1和DA3肿瘤细胞在体外对Fas介导的裂解或脾NK细胞以穿孔素依赖性方式敏感。穿孔素缺陷的NK细胞不能裂解这些肿瘤，穿孔素缺陷的小鼠在排斥肿瘤细胞向肺转移方面比野生型小鼠效率低10至100倍。Fas配体突变的gld小鼠对肿瘤转移具有未受损的保护作用。NK亚群的耗竭导致转移灶数量比穿孔素缺陷小鼠中观察到的更多，这表明NK细胞的穿孔素非依赖性效应功能也可能有助于预防肿瘤转移。
