Dendritic cells: a novel therapeutic modality.

Dendritic cells (DC) are bone marrow derived professional antigen presenting cells (APC). Since the recognition of DC in lymphoid organs in 1973 [1] remarkable progress has been made in the understanding of their origin and their important role in the immune system. DC comprise a heterogeneous population, with different properties and characteristics. Langerhans cells, the ¢rst DC described, are widely distributed in human skin, oesophagus, cervix and buccal epithelia. Other DC have been reported in the dermis of the skin and in the interstitium of all tissues with exception of the brain (interstitial or tissue DC). They may also be found in the a¡erent lymph (veiled DC), in the cortical zones of the lymph nodes and in the spleen (interdigitating DC) [2]. The primary function of DC is to act as sentinels between the outside world and the body. For this purpose they possess a high capacity for antigen uptake and processing. Following antigen uptake and in the presence of appropriate `danger signals', DC migrate rapidly toT-cell areas in the lymph nodes where they can initiate an immune response [3]. In contrast to other members of the APC family (macrophages, B cells) DC are capable of inducing primary immune responses by the activation of na|« ve T cells [4]. Escape from immune surveillance by cytotoxic T cells (CTL) is a fundamental feature of tumours and contributes to their uncontrolled growth. Although tumour cells express tumour antigens, antigen presentation by tumour cells to T cells is an ine¡ective process. The number of antigenic peptide containing major histocompatibility complex (MHC) molecules on tumour cells and the chance that their recognition by sparse antigen speci¢c T cells will occur is very low. Moreover, tumour cells mostly lack co-stimulatory surface molecules necessary for stimulation and clonal expansion of T cells. Indeed, antigen presentation in the absence of co-stimulatory signals can lead to T-cell anergy rather than to T-cell activation. The central role of DC in the initiation of immune responses and new methods for the ex vivo expansion of DC creates possibilities for the development of novel immunotherapeutic strategies against tumours and other diseases. This makes the ex vivo generation of DC an interesting tool in the development of vaccines for cancer patients. This review outlines recent progress in the understanding of the place of DC within the haematopoietic lineage, their role in antitumour immunity and new experimental approaches for the application of DC in the immunotherapy of cancer patients.