In DC-based immunotherapy, it is occasionally difficult to obtain a sufficient number of quality-guaranteed DC for some patient groups, such as: (1) paediatric cancer patients, who are too

small to receive leukapheresis for DC preparation [20], (2) cancer patients with pancytopaenia owing to cachexia or basal disease-related factors such as liver cirrhosis or (3) patients with haematological malignancy, in whom peripheral blood may be contaminated with a large number of viable malignant cells. In such patients, allogeneic DC may be an alternative source. It has been suggested that the host alloresponse to the injected DC may actually facilitate the antitumour response AZD1208 chemical structure and that their alloantigens may work as helper antigens [21]. However, this theory is controversial [22, 23]. Moreover, Daporinad some preclinical studies using murine s.c. tumour models have shown that s.c. immunization using fully allogeneic DC failed to induce antitumour effects [14, 24]; thus, the use of allogeneic DC in DC-based immunotherapy may be limited. When allogeneic DC are used for cancer immunotherapy, three important factors must be considered. First,

the major histocompatibility complex (MHC) incompatibility of the DC used may be the most important factor for priming the MHC-restricted TAA-specific CD8+ T cells [25, 26] because during T-cell development, the host T cells acquire MHC restriction because of positive selection [27] by somatic cells (cortical thymic epithelial cells (cTECs), which are the crucial APC for expressing the MHC), rather than

haematopoietic cells [27]. Second, the survival of injected allogeneic DC may be shortened by T-cell-mediated rejection, and this may have an effect on the resulting antitumour response because DC survival is an important factor in priming antigen-specific T-cell responses. Third, it is not known whether host-derived pAPC can function in an antitumour capacity in DC-based immunotherapy, especially via the i.t. injection route. Until Loperamide now, no experimental model has been developed that assesses these factors individually, and it is unclear which of the factors, and to what degree, will affect the antitumour responses of allogeneic DC. It is also unclear which injection route is most preferable when using allogeneic DC. Here, we aimed at evaluating the availability of allogeneic DC for DC-based immunotherapy and to elucidate the mechanism for the antitumour effect, focusing on the three important factors related to allogeneic DC. We demonstrate that s.c. immunization using semi- or fully allogeneic DC pulsed with tumour lysate has a limited antitumour effect and does not induce a significant number of IFN-γ-producing tumour-specific CD8+ T cells. When semi-allogeneic DC were injected via an i.t. injection route, we observed the induction of an efficient antitumour response and a significant tumour-specific CD8+ T-cell response.