Local administration of dendritic cells inhibits established breast tumor growth: Implications for apoptosis-inducing agents

Dendritic cells (DCs) can efficiently acquire foreign antigen(s) from apopt otic cells and induce MHC class I-restricted, antigen-specific CTLs. An acc umulation of DCs within solid tumor masses in situ has been associated indi rectly with a more favorable prognosis. Therefore, DCs may offer an efficie nt means for triggering immune responses within tumors, particularly in tho se masses containing significant apoptosis. We examined whether delivery of DCs could, alone, impact on the progressive growth of a tumor with a relat ively high apoptotic index. We detected significant early apoptosis within the mass of a s.c. growing murine MT-901 breast carcinoma. DCs could effici ently engulf MT-901 tumor apoptotic cells in vitro. Intratumoral injections of syngeneic but not allo geneic DCs resulted in significant inhibition of MT-901 tumor growth, Histological examination of the tumor revealed intens e mononuclear cell infiltration during and after DC injections. Tumor growt h inhibition was relatively radiosensitive and dependent on host derived CD 8(+) T cells. The baseline level of tumor apoptosis could be increased subs tantially by tumor necrosis factor a:administration, leading to a greater D C-mediated antitumor effect. The antitumor effect could also be enhanced by first pulsing DCs with the foreign helper protein, keyhole limpet hemocyan in, prior to intratumoral delivery and combining it with the systemic admin istration of interleukin 2. Splenocytes from treated animals showed heighte ned levels of specific CTL activity and production of cytokines. The level of in situ tumor apoptosis appears to play a critical role in DC-mediated a ntitumor effects. The potential implication of these findings in DC-based t umor therapy strategies is discussed.