Tumor-Derived Exosomes and Antigen Presentation

[Guest guest]

Immunology: Presentation is everything

EZZIE HUTCHINSON

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, ce 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.

ORIGINAL RESEARCH PAPER

Malignant effusions and immunogenic tumour-derived

exosomes.

Andre, F. et al.

Lancet 360, 295–305 (2002)

| PubMed |

__________________________________________________

- We Remember

9-11: A tribute to the more than 3,000 lives lost

http://dir.remember./tribute