4, right-hand graph and Fig. 1C). We also studied the IFN-γ production by tumour-infiltrating CD4+ and CD8+ T cells Copanlisib research buy and found this to be correlated with the suppression of tumour growth after ITADT in each of the experimental groups (data not shown). These results suggest that not only the injected syngeneic DC but also host-derived in situ APC functioned well as pAPC in ITADT, resulting in an efficient antitumour effect. Therefore, ITADT using MHC-incompatible allogeneic DC resulted in an efficient
antitumour effect if there was no rejection of the injected DC, and these effects were likely mediated indirectly via the MHC-compatible in situ pAPC of the host. Taken together, all three factors — [(1) survival of injected DC, (2) MHC compatibility of the injected DC and (3) function of host-derived pAPC] – affected the antitumour response induced by ITADT, but the survival time of the injected DC was the most important factor when using allogeneic DC. As described earlier, the host-derived pAPC functioned so well in ITADT that semi-allogeneic DC showed efficient antitumour INCB024360 concentration effects. Even fully allogeneic DC had significant antitumour effects if the alloresponse of the host was abrogated. We next investigated whether semi-allogeneic DC or fully allogeneic DC would have an antitumour effect if injected subcutaneously at sites distant from
the tumour (we refer to this as SCDT). In this case, tumour-associated host-derived pAPC could not contribute to any antitumour effect by priming TAA-specific T cells. In addition, we also investigated the antitumour effects of SCDT using syngeneic DC and compared the results with those of ITADT using syngeneic DC. For SCDT, we used DC that had been pulsed with tumour lysate. ITADT using syngeneic BL6 DC showed an efficient antitumour clonidine effect, resulting in significant suppression
of tumour growth (4/5 tumours eradicated) and significantly improved survival rates compared with PBS-treated controls (Fig. 5A,B, P < 0.01). SCDT using syngeneic BL6 DC also showed a significant antitumour effect compared with controls (Fig. 5A,B, P < 0.05). However, the antitumour effect observed in SCDT using BL6 DC was significantly weaker than that of ITADT using BL6 DC, and no tumour eradication was observed. Additionally, the survival rates in the SCDT group using BL6 DC were significantly worse compared with those in the ITADT group using BL6 DC (Fig 5A,B, P < 0.01). It was noted that SCDT using either semi-allogeneic BDF1 DC or fully allogeneic DBA/2 DC did not show a significant antitumour effect (Fig. 5A,B). We also investigated the effects of SCDT and ITADT against CT26 tumours. SCDT using syngeneic B/c DC had a significant antitumour effect in terms of tumour growth suppression and prolonged survival times relative to PBS controls (Fig. 5C,D, P < 0.01).