The evolving role of dendritic cells in cancer therapy.
BACKGROUND
Dendritic cells (DC) are a clear choice for use in cancer immunotherapy, and much research has focused on generating DC for clinical use. Although DC therapy has been successful in inducing specific anti-tumour immune responses, these have rarely translated into clinical efficacy.


METHODS
We examine some of the components of generating DC for therapy, including their culture, antigen loading and delivery, and discuss why DC therapy has not yet delivered substantial clinical benefit. We also examine more novel approaches, such as the potential for combination DC-based immunomodulatory strategies.


RESULTS
Given the highly immunosuppressive tumour environment, many of the approaches to DC vaccination are unlikely to result in effective therapy, as even successfully primed T cells may fail to infiltrate tumours or be anergized after entry. Broader approaches against multiple tumour-associated antigens in the context of overcoming tumour immune suppression are likely to prove more successful. The combination of oncolytic viral therapy with DC vaccines may promote an inflammatory tumour environment, inducing optimal DC activation, T cell priming and effective therapy.


CONCLUSIONS
Evolving DC-based therapeutic strategies addressing multiple components of tumour-immune system interactions may yield substantial benefits for patients.
University of Leeds, Leeds Institute of Molecular Medicine, CRUK Clinical Centre, Beckett Street, Leeds, UK.
E J
EJ
Ilett
R J D
RJ
Prestwich
A A
AA
Melcher
D017690:Cell Transplantation; D003713:Dendritic Cells / Q000166:cytology* / Q000276:immunology; D006801:Humans; D009369:Neoplasms / Q000276:immunology / Q000628:therapy*