Immunological ignorance of solid tumors.

Abstract

Many peripheral solid tumors such as sarcomas and carcinomas express tumor-specific antigens that can serve as targets for immune effector T cells. Nevertheless, the immune surveillance against clinically manifest carcinomas and sarcomas seems relatively inefficient. Naïve cytotoxic T cells are activated exclusively in secondary lymphoid organs including the spleen and lymph nodes. Tumor antigen might be either cross-presented to naïve cytotoxic T cells by professional antigen-presenting cells (pAPC), or presented directly by tumor cells that migrated to secondary lymphoid organs. Direct priming is quite inefficient during early tumor development because metastasis to lymphoid organs is usually limited to advanced stage diseases. Similarly, the process of cross-priming by pAPC seems to depend on relatively large antigen amounts and on maturation stimuli for dendritic cells, and both requirements may be limiting during initial tumorigenesis. Therefore, the immunosurveillance of solid tumors may fail because they are ignored for too long by the immune system. However, these situations may prove promising for the induction of tumor-specific T cell immunity by vaccination, as the T cell repertoire against these antigens has a naïve phenotype and is not yet affected by tolerance mechanisms.