The correlation of immunologic responses to tumor lysates in vitro with DTH responses in vivo in patients receiving the combination therapy of tumor lysate-pulsed dendritic cells and an adoptive transfer of T cells Free

4248

Purpose: We sought to determine the correlation between immunologic and DTH responses to tumor lysates in patients (pts) treated with tumor lysate-pulsed dendritic cells (TP-DC). Patient and Methods: Pts received TP-DC intradermally (i.d.) 4 times every 3 weeks with T cells activated with interleukin-2 and antibody to CD3. Four weeks after the final treatment, immunologic responses of pts to tumor lysates in vitro were analyzed with IFN-gamma production, the absolute number of peripheral blood lymphocytes (PBL) and the phenotype of PBL. Furthermore, DTH responses of pts to tumor lysates in vivo were assessed. Every 3 months after the final treatment, immunologic and DTH responses were followed in pts with the positive DTH. Results: Pts with the positive DTH to tumor lysates after the fourth treatment revealed the increase in the number of PBL compared to those with the negative DTH (from 24.9% to 44.8% v from 24.2% to 29.3%, respectively; p<0.0001). In 4 of 6 pts with the positive DTH, the duration of the positive DTH was within 6 months. A significant correlation between the number of PBL and the DTH responses was observed. Twelve months after the final treatment, 5 of 6 pts who had previously shown the positive DTH experienced the negative DTH with the decrease in the number of PBL. Furthermore, all pts with the positive DTH revealed the significant IFN-gamma production by T cells stimulated with tumor lysate-pulsed DC. The Correlation of the DTH with the IFN-gamma production by T cells was observed. In adjuvant settings, pts with the positive DTH experienced less tumor relapse compared to those with the negative DTH. Conclusion: The positive DTH in vivo may indicate the increase in the number of tumor specific T cells. The DTH responses following the treatments demonstrated that the duration of T cell-memory was within 6 months associated with the decrease of the tumor specific-IFN-gamma production by T cells. Based on these findings, the DTH responses may be a useful guide to assess patients for the immunological and clinical responses.