IN-VIVO PRIMING OF 2 DISTINCT ANTITUMOR EFFECTOR POPULATIONS - THE ROLE OF MHC CLASS-I EXPRESSION

Downregulation of major histocompatibility complex (MHC) class I expre ssion is an important mechanism by which tumors evade classical T cell -dependent immune responses. Therefore, a system was designed to evalu ate parameters for active immunization against MHC class I-tumors. Mic e were capable of rejecting a MHC class 1- tumor challenge after immun ization with an irradiated granulocyte/macrophage colony-stimulating f actor (GM-CSF) transduced MHC class 1- tumor vaccine. This response wa s critically dependent on CD4+ T cells and natural killer (NK) cells, but minimally on CD8+ T cells. A strong protective response against MH C class I+ variants of the tumor could be elicited when mice were immu nized with irradiated MHC class I + GM-CSF-secreting tumor cells. This response required CD4 + and CD8 + T cells, and in addition, eliminati on of NK cells resulted in outgrowth of tumors that had lost expressio n of at least one MHC class I gene. Finally, class I MHC expression on the vaccinating cells inhibited the response generated against a MHC class 1- tumor challenge. These results demonstrate that the host is c apable of being immunized against a tumor that has lost MHC class I ex pression and reveal conditions under which distinct effector cells pla y a role in the systemic antitumor immune response.