Malignant effusions and immunogenic tumour-derived exosomes.

Area of Science:

• Immunology
• Oncology
• Cell Biology

Background:

• Tumour-derived exosomes are vesicles released by cancer cells.
• Exosomes' role in vivo and their potential for cancer immunotherapy were investigated.
• Malignant effusions were examined for the presence of tumour exosomes.

Purpose of the Study:

• To determine if tumour exosomes in malignant effusions can induce tumour-specific T cells.
• To explore the potential of ascites exosomes as a source of tumour antigens for cancer vaccines.

Main Methods:

• Exosomes were isolated from 11 malignant effusions using ultracentrifugation.
• Exosome characterization involved Western blot, immunoelectron microscopy, and in-vitro T cell stimulation.
• Autologous dendritic cells were pulsed with ascites exosomes to expand tumour-specific T cells.

Main Results:

• Malignant effusions contain numerous exosomes (mean diameter 80 nm) expressing MHC class-I, CD81, and tumour antigens (Her2/Neu, Mart1, TRP, gp100).
• Melanoma exosomes delivered Mart1 tumour antigens to dendritic cells for T cell cross-presentation.
• Tumour-specific T cells were expanded in 7/9 cancer patients by pulsing autologous dendritic cells with ascites exosomes.

Conclusions:

• Tumour exosomes accumulate in ascites from cancer patients.
• Ascites exosomes represent a novel source of tumour-rejection antigens.
• These findings suggest new strategies for developing cancer immunotherapies.