Immune surveillance against a solid tumor fails because of immunological ignorance

Many peripheral solid tumors such as sarcomas and carcinomas express tumor- specific antigens that can serve as targets for immune effector T cells, Ne vertheless, overall immune surveillance against such tumors seems relativel y inefficient. We studied immune surveillance against a s.c. sarcoma expres sing a characterized viral tumor antigen. Surprisingly, the tumor cells wer e capable of inducing a protective cytotoxic T cell response if transferred as a single-cell suspension. However, if they were transplanted as small t umor pieces, tumors readily grew. Tumor growth correlated strictly with (i) failure of tumor cells to reach the draining lymph nodes and (ii) absence of primed cytotoxic T cells. Cytotoxic T cells were not tolerant or deleted because a tumor antigen-specific cytotoxic T cell response was readily ind uced in lymphoid tissue by immunization with virus or with tumor cells even in the presence of large tumors. Established tumors were rejected by vacci ne-induced effector T cells if effector T cells were maintained by prolonge d or repetitive vaccination, but not by single-dose vaccination. Thus, in a ddition to several other tumor-promoting parameters, some antigenic periphe ral sarcomas-and probably carcinomas-may grow not because they anergize or tolerize tumor-specific T cells, but because such tumors are immunologicall y dealt with as if they were in a so-called immunologically privileged site and are ignored for too long.