MHC imbalance and metastatic spread in Lewis lung carcinoma clones

Imbalance in the K b and D b region encoded molecules is observed in Lewis lung carcinoma clones. The uncloned metastatic population and the D122 high‐metastatic clone show no expression of H‐2K b products, while the non‐metastatic A9 clone expresses K b products. Twenty‐nine new subclones of 3LL and A9 were analyzed for D‐end and K‐end membrane expression, primary growth rate and metastatic spread. We show that the imbalance in H‐2K b to H‐2D b is correlated with metastatic properties of a given clone, but local tumor growth is not. A “low K b /low D 9 ” phenotype is nonmetastatic as is a “high K b /high D b ” phenotype; a “low K b /high D b ” is highly metastatic and a “medium K b /high D b ” is moderately metastatic. We find support for this notion of imbalance in experiments on MHC modulation by interferon and retinoic acid. Interferon increases both K b and D b expression of A9 and D122 clones yet the net increase of D b was greater than K b . This was associated with an increase in metastasis formation. Retinoic acid increases the expression of the D b gene product on the nonmetastatic A9, clone, without apparent changes in K b expression. This treatment shifts the A9 to a high‐metastatic phenotype. The significance of this imbalance to the tumor — host relationship is discussed.