Immunoselection by T lymphocytes generates repeated mhc class I-deficient metastatic tumor variants

Alteration of MHC class I molecule expression is a widespread mechanism use d by tumor cells to evade T cell responses, It has long been proposed that the origin of these MHC class I-negative or -deficient tumor variants is T cell immune selection. However, there are no experimental or clinical data to substantiate this hypothesis, and this issue is currently the subject of debate. Here we report that an H-2 class I-negative fibrosarcoma tumor clo ne generated MHC class I-negative spontaneous lung metastases in immunocomp etent syngeneic BALB/c mice. Interestingly, the same B9 done generated MHC class I-positive metastatic nodes, under basal conditions, in athymic nu/nu BALB/c mice. This phenomenon was observed in the metastatic nodules genera ted after a period of in vivo growth but not in the primary tumors growing: locally in the footpad. These findings support the hypothesis that the H-2 phenotype of metastatic nodes is influenced by the T cell repertoire of th e host, since in the absence of this T cell pressure (i.e., in nude mice) t he metastatic nodes 'recovered' H-2 class I expression. In addition, 2 diff erent phenotypes were found when the metastatic nodules obtained from immun ocompetent mice were treated with IFN-gamma, One phenotype, present in 83% of the colonies, was characterized by resistance of the L-d molecule to IFN -gamma induction, due to a deletion involving the L-d gene. The second phen otype (17% of the colonies) was similar to the original B9 clone and was ch aracterized by the response of K, D and L class I genes to IFN-gamma. These data provide evidence that the changes in MHC class I expression during tu mor development might not be random but could be predictable. (C) 2001 Wile y-Liss, Inc.