Overcoming self-tolerance to tumour cells.
Over the past decade, immunotherapy has emerged as a promising alternative form of cancer treatment with the potential to eradicate tumour metastasis. However, its curative potential is in general limited by peripheral tolerance mechanisms and the elimination of self-reactive T cells via thymic negative selection. Unlike infectious challenges, tumour cells arise endogenously, and therefore the majority of tumour antigens are recognized as self. Under appropriate conditions, however, tumour reacting T cells can be activated through a mechanism of molecular mimicry, which involves the recognition of cross reactive foreign antigens mimicking tumour antigens. Moreover, dendritic cells can be reprogrammed by RNA interference to present self-antigens and activate anti-tumour T cells. This review highlights some of the strategies used to break self-tolerance against solid and blood tumour cells. Also, the possibility of reprogramming DC and/or lymphocyte functions using small interfering RNAi (siRNA) is discussed.
Sioud
Mouldy
M
Department of Immunology, Institute for Cancer Research, Rikshospitalet-Radiumhospitalet, University Hospital, Oslo, Norway.
D000818:Animals; D000951:Antigens, Neoplasm / Q000276:immunology; D015551:Autoimmunity / Q000276:immunology; D000939:Epitopes / Q000276:immunology; D006801:Humans; D008213:Lymphocyte Activation / Q000276:immunology; D009369:Neoplasms / Q000276:immunology*; D017634:Self Tolerance / Q000276:immunology*
D000951:Antigens, Neoplasm; D000939:Epitopes