In vivo priming of two distinct antitumor effector populations: The role of MHC class I expression

Downregulation of major histocompatibility complex (MHC) class I expression is an important mechanism by which tumors evade classical T cell- dependent immune responses. Therefore, a system was designed to evaluate parameters for active immunization against MHC class I^- tumors. Mice were capable of rejecting a MHC class I^- tumor challenge after immunization with an irradiated granulocyte/macrophage colony-stimulating factor (GM-CSF) transduced MHC class I^- tumor vaccine. This response was critically dependent on CD4⁺ T cells and natural killer (NK) cells, but minimally on CD8⁺ T cells. A strong protective response against MHC class I⁺ variants of the tumor could be elicited when mice were immunized with irradiated MHC class I⁺ GM-CSF-secreting tumor cells. This response required CD4⁺ and CD8⁺ T cells, and in addition, elimination of NK cells resulted in outgrowth of tumors that had lost expression 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 I^- tumor challenge. These results demonstrate that the host is capable of being immunized against a tumor that has lost MHC class I expression and reveal conditions under which distinct effector cells play a role in the systemic antitumor immune response.