In the case of DC-based immunotherapy using non-hybrid DC, see more it was reported that reduced survival rates of subcutaneously injected DC because of CTL responses against even a single epitope limited their efficacy to prime specific T-cell responses [32]. Therefore, in general, it appears that alloresponsive T cells interfere with the TAA-specific T-cell priming capacity of the injected allogeneic DC. The results of this study suggest that ITADT should be selected when

semi-allogeneic DC are used for immunotherapy rather than SCDT. We also suggest that fully allogeneic DC are of limited use for DC-based immunotherapy, even in ITADT, when the alloresponse to injected DC cannot be controlled. It is unclear why semi-allogeneic DC were rejected more slowly by host T-cell responses than fully allogeneic DC, especially at the tumour Cilomilast site. Generally, T-cell-mediated rejection of semi-allogeneic haematopoietic cells is milder than that of fully allogeneic cells, and this phenomenon is largely dependent on regulatory T cells (Tregs), especially ‘naturally occurring’ Tregs [43–45]. Fucs et al. [44] reported that B/c recipient Tregs could suppress B/c -derived T-cell-mediated rejection of BL6 x B/c (H-2b/d) F1 splenocytes, but not BL6 (H-2b) splenocytes, suggesting that expression of both H-2b and H-2d on the same cells was required for Treg-mediated suppression of the rejection of BL6 (H-2b)-derived

donor major and minor alloantigens. It is likely that the expression of recipient-derived MHC class II (which can be recognized by recipient Tregs) is essential for this suppression [45]. Because Tregs can accumulate at the tumour site (Okano S. unpublished observation) [46] and also suppress CTL-mediated effector function [47], prolonged survival of intratumourally injected BDF1 DC may be attributed to Treg-mediated suppression of the rejection response. In conclusion, ITADT using semi-allogeneic DC can induce an efficient antitumour response in cooperation with host-derived pAPC (probably tumour-associated pAPC). These results

can be informative for patients from whom large numbers of DC are difficult to obtain. The authors thank Kazunori Nakagawa for support of this study. This work was supported from by a Grant-in-Aid from the Japan Society for the Promotion of Science (S. O. 17590350). The authors have no conflicts of interest to declare. Figure S1 ITADT using syngeneic or semi-allogeneic DCs shows significant antitumour effects. (A) The changes in tumour volume over time observed in individual mice are indicated in the experimental groups shown in Fig. 1A,B. The number of tumours eradicated within each group is shown below the line graphs (rejection number). Crosses indicate the death of individual mice at the marked time points. Data were obtained from three separate experiments.