[Mechanisms of tumor escape from immunologic response].

INTRODUCTION

The rationale for immune control of cancer is now better defined via the immunovirology of transforming viruses, definition of human tumor antigens recognized by T-lymphocytes, and cellular and humoral components of the anticancer response. Nonetheless tumors can escape from immune surveillance. To better define immunomodulation strategies, we describe some of the various strategies developed by transformed cells to evade the immune response.

CURRENT KNOWLEDGE AND KEY POINTS

Both the lack of specific tumor antigen and down-regulation of major histocompatibility complex (MHC) molecule expression hamper recognition of neoplastic cells by T-lymphocytes. In presence of defective expression of ligands for the T-cell co-stimulatory receptors, tumor recognition may lead to the development of tolerance instead of specific cytotoxic activity. Tumor cell counter-attack against effector T-cells has also been described, using either inhibitory cytokines (IL-10), apoptosis induction (via Fas signalling), functional inactivation (disruption of normal CD40/CD40 ligand interactions), or induction of anergy.

FUTURE PROSPECTS AND PROJECTS

Despite the many different mechanisms of tumor escape, the immune system has developed efficient counter-attacks. For instance, natural killer cells may detect and destroy tumor cells that lack class 1 MHC molecules and thus escape from specific T-lymphocyte cytolysis. Moreover, immunogenicity can be restored, at least in vitro, by different means such as tumor cell stimulation by cytokines or CD40, suggesting that therapeutic strategies will soon be developed in order to stimulate an efficient antitumoral immune response.