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Tumour Immunogenicity, Antigen Presentation, and Immunological Barriers in Cancer Immunotherapy

DOI: 10.1155/2014/734515

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Abstract:

Since the beginning of the 20th century, scientists have tried to stimulate the antitumour activities of the immune system to fight against cancer. However, the scientific effort devoted on the development of cancer immunotherapy has not been translated into the expected clinical success. On the contrary, classical antineoplastic treatments such as surgery, radiotherapy, and chemotherapy are the first line of treatment. Nevertheless, there is compelling evidence on the immunogenicity of cancer cells and the capacity of the immune system to expand cancer-specific effector cytotoxic T cells. However, the effective activation of anticancer T cell responses strongly depends on efficient tumour antigen presentation from professional antigen presenting cells such as dendritic cells (DCs). Several strategies have been used to boost DC antigen presenting functions, but at the end cancer immunotherapy is not as effective as would be expected according to preclinical models. In this review, we comment on these discrepancies, focusing our attention on the contribution of regulatory T cells and myeloid-derived suppressor cells to the lack of therapeutic success of DC-based cancer immunotherapy. 1. Introduction: Vaccines Infectious Diseases and Cancer Not so long ago, I had a conversation with a colleague of mine about our differing research interests. He asked me why I was so much interested in cancer research and not that keen on infectious diseases. This particular question made me think about my motives for working in cancer research. Cancer is in many cases an “adult” noncontagious disease (with exceptions), while infectious diseases can attack anyone at any time. In addition, infectious agents are highly contagious and new ones arise from time to time [1, 2]. He argued that compared to cancer, infectious diseases are a much higher health burden worldwide. After this conversation I quickly looked at the statistics and according to Cancer Research UK (http://www.cancerresearchuk.org), there were about 7.6 million deaths from cancer in 2008. Then I looked at the deaths caused by infectious diseases, and according to the World Health Organisation (WHO, http://www.who.int/en/) about 13 million deaths (of all ages) were caused by infectious diseases in 1998. Even though the data was not that recent, I concluded that the first premise on health burden might not be completely accurate. However, ultimately that was not the reason I was looking for. Therefore, why is cancer so fascinating that attracts so much scientific and medical efforts? Among the nonmedical

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