Selective upregulation of MHC class I expression in metastatic colonies derived from tumor clones of a murine fibrosarcoma

Eighteen metastatic nodes derived from the wild-type (GR9) and from 4 diffe rent clones (G2, D8, B10, and B9) obtained from a fibrosarcoma were analyze d for H-2 class I and II expression, as well as for adhesion molecules (CD3 4, CD11b, CD18, CD49, and CD54). When metastatic nodes were cultured, typed for H-2 antigens, and compared with the H-2 expression of the inducing tum or cell, H-2 K-d and D-d class I expression was greater in most nodes analy zed. In contrast, the L-d molecule remained negative, or showed a minor inc rease. Class II expression was negative in the wild-type and the tumor clon es, and remained so in the metastatic colonies. Analysis of the adhesion mo lecules revealed no differences between the inducing tumor cells and the me tastatic nodes. The only molecule expressed was CD34, which was present in all cells studied and was also inducible by interferon-gamma. The increase in H-2K and H-2D expression was associated with resistance to natural kille r cytotoxicity, as observed in the G2 tumor clone and some autologous metas tases, such as B9MP2, G2MK2, and G2ML1. In three independent clones of this tumor system (D8, BIOMP6, and B9MP6) we found that tumor cells treated wit h interferon-gamma had the same altered phenotype, i.e., a selective lack o f response of the L-d molecule to induction. These findings add a cautionar y note to the well-established idea that tumor cells may lose all class I a ntigens during tumor progression, and suggest that sometimes this may not b e the case. The selective downregulation of L-d and upregulation of K-d and D-d class I expression may give some tumor cells means of escaping both cy totoxic lymphocyte and natural killer immune surveillance.