To date TAAs matching almost all of these criteria are the human papillomavirus (HPV) E6 and E7 proteins. The association of HPV with HNSCC and the utilisation of viral oncoprotein for immunotherapy has been reviewed elsewhere [6]. Briefly HPV is associated with approximately 20–25% of all HNSCC and up to 60–70% of those tumours localized to the oropharynx,

in particular tonsil [7]; the HPV type 16 has been found in more than 90% of HPV-positive HNSCC; the E6 and E7 proteins are constitutively expressed and maintained during the MEK pathway HPV-associated carcinogenesis; and the viral oncoproteins are foreign antigens and, therefore, are highly immunogenic. Beside the matching to an ideal TAA the HPV E6 and E7 proteins serve as model antigens for the development of immunotherapy and since HPV type 16 is also associated with cervical and anogenital cancers, the p38 MAPK signaling same vaccine strategies developed to prevent (already in clinical use) and/or to treat HPV-associated cervical and anogenital cancers can also be used in head and neck cancers [for review see [6, 8]]. Nevertheless these Vorinostat in vivo oncoproteins account for only 20%

of HNSCC and enforces must be done to identify other TAAs in the remaining HNSCC matching closely all the above mentioned criteria. In this filed an enormous work has been done but before some of these TAAs becomes valid therapeutic vaccine other hurdles must be overcome, the tumour immune escape and tumour tolerance. Tumour immune escape and tolerance The discovery of so powerful TAAs in HNSCC is giving substantial basis heptaminol for efficacious and less toxic treatments, but in the mean time HNSCC as other tumours participates in tumour immune escape through various mechanisms: i) it disrupts antigen processing and presentation machinery by altering the MHC class I and TAP 1–2 expression;   ii) it recruits immunosuppressive Treg to dampen effector T-cell activity,   iii) by chemokine production it alters T-cell homeostasis

increasing the sensitivity of effector T cells to apoptosis.   Downregulation of antigen-processing machinery (APM) components, such as TAP 1/2 and MHC class I antigens, renders ineffective the recognition by CTL in HNSCC. More than 50% of primary and metastatic lesions showed MHC class I antigen loss [9]. Interestingly, interferon-γ (IFN-γ), which functions to up-regulate APM and MHC molecules, can restore in vitro the ability of specific CTLs to recognize their tumour cell targets and subsequently to lyse them [10, 11]. Thus in a therapeutic setting clinical efforts must be undertaken in order to restore APM and MHC class I antigen expression in HNSCC. The complex biology of CD4+CD25+FoxP3+ regulatory T cells (Treg), which function to downmodulate immune responses and have enormous implications on the development of cancer immunotherapies, is far to be fully understood.