If information piles up and is not passed on to the right department, what are the chances that it will elicit a response or be acted on? Nil. Likewise, tumours might not actually lack tumour antigens but, if these antigens are not presented effectively to the immune system, activation of the immune response is unlikely. In the 27 July issue of The Lancet, Laurence Zitvogel and coworkers report a new source of tumour antigens — exosomes in tumour ascites — that enable loading of antigen-presenting cells, dendritic cells (DCs), to activate cytotoxic T cells and elicit an immune response against tumours, even if the tumours themselves are poorly immunogenic.

Tumour-derived exosomes are small vesicles that carry molecules that are involved in antigen presentation, such as MHC class I molecules, heat-shock proteins, tetraspanins and tumour antigens. Zitvogel et al. have previously shown that exosomes derived in cell culture are immunogenic, and the present study indicates that exosomes can also be isolated in large quantities from tumour ascites from patients and that these are also immunogenic. For instance, monocyte-derived DCs loaded with ascitis exosomes from a patient with Mart1-positive melanoma induce differentiation and expansion of tumour-specific cytotoxic T cells that are derived from these patients, even if the tumours themselves are poorly immunogenic. The authors examined ascites from the peritoneal fluid of 10 other patients who had malignant effusions and showed similar reponses in ovarian and breast cancer, in which the exosomes expressed ERBB2 (also known as HER2/neu).

A comparison between primary tumour cell cultures and ascites showed that many more exosomes were harvested from ascitic fluids, and T-cell responses were easier to stimulate with exosomes from tumour ascites.

So how can this information be used further? Tumour-derived exosomes in ascites could be used to generate large numbers of tumour-specific T cells for adoptive immunity and could be used in vaccines. Whether exosomes will be clinically applicable for immunization against cancer, and whether they will help identify tumour antigens, are questions that are yet to be answered.