Abstract

The immune surveillance theory postulates that spontaneous tumors are normally rejected by the immune system and appear only when they override host‐immune recognition and rejection mechanisms. The present mini‐review describes a spontaneous tumor system, the reticulum cell sarcomas (RCS) in SJL/J mice, that is dependent on host tumor‐specific immune lymphocytes for growth. This continuous tumor‐specific response results in tumor progression and death of the host. This tumor system contradicts the basic concept of immune surveillance. We propose as an explanation that some highly antigenic tumors, like the RCS, may have evolved in a non‐autonomous fashion but, nevertheless, have lost regulatory controls of cell proliferation. In the RCS system, the tumor expresses Class II MHC I‐E like specificities that are not expressed on the host cells and which selectively stimulate a subpopulation of I‐E specific T cells, the Vβ17a+ clonotype, leading to their expansion and continuous nurturing of the tumor via secreted lymphokines. This neoantigenic stimulation bypasses the tumor regulatory response that might have resulted if the tumor had not expressed neo‐antigens. Furthermore, passive administration of anti‐clonotypic antibody to tumor‐bearing mice results in tumor regression and long‐term survival through removal of the tumor reactive T cells. Thus, in this tumor system, immunosuppressive treatments are the prescription for tumor rejection.