Tumor escape from immune surveillance

Introduction. - The rationale for immune control of cancer is now better de fined via the immunovirology of transforming viruses, definition of human t umor antigens recognized by T-lymphocytes, and cellular and humoral compone nts of the anticancer response. Nonetheless tumors can escape from immune s urveillance. To better define immunomodulation strategies, we describe some of the various strategies developed by transformed cells to evade the immu ne response. Current knowledge and key points. - Both the lack of specific tumor antigen and down-regulation of major histocompatibility complex (MHC) molecule exp ression hamper recognition of neoplastic cells by T-lymphocytes. In presenc e of defective expression of ligands for the T-cell co-stimulatory receptor s, tumor recognition may lead to the development of tolerance instead of sp ecific cytotoxic activity. Tumor cell counter-attack against effector T-cel ls has also been described, using either inhibitory cytokines (IL-10), apop tosis induction (via Fas signalling), functional inactivation (disruption o f normal CD40/CD40 ligand interactions), or induction of anergy. Future prospects and projects. - Despite the many different mechanisms of t umor escape, the immune system has developed efficient counter-attacks. For instance, natural killer cells may detect and destroy tumor cells that lac k class I MHC molecules and thus escape from specific T-lymphocyte cytolysi s. Moreover, immunogenicity can be restored, at least in vitro, by differen t means such as tumor cell stimulation by cytokines or CD40, suggesting tha t therapeutic strategies will soon be developed in order to stimulate an ef ficient antitumoral immune response. (C) 1999 Elsevier, Paris.