A Fundamental Research Of Specific Anti-tumor Immunal Effects Of DC Sensitized In Vivo

Dendritic cells( DC)is the most powerful antigen-presenting cells (APC), which can phagocytes many kinds of antigen, and expresses lots of MHC, costimulatory molecules, adhesion molecule, and stimulates cytotoxicitic T cells to kill tumor cells. With former research we knew that the DC sensitized by many tumor antigen can induce effective CTL's activity, and injection of these cells which loaded tumor antigen into patients, showed a better anti-tumor effect, especially the DC sensitized in vitro. Low dose chemotherapy is used clinically for its slim side effect, low dose of %-Fu and DDP are administrated in gastrointestinal tumor, head and neck tumor, liver cancer, breast cancer and bladder caner, a better result was achieved. Prupose: we administrated DC intratumorally after the apoptosis induced by low dose chemotharepy, and investigated the effect of apoptosic tumor cells on DC, further the probability of DC's sensitized in vivo, try to find new method in biotherapy to tumor. Methods: We injected MFC into 615 mice to get tumor model, and induced immature DC from bone marrow in vitro by rmGM-CSF and rmIL-4. All animals were divided into 4 groups as: low dose chemotherapy alone(5-Fu, DDP), DC alone, both low dose chemotherapy(5-Fu, DDP) and DC, control. Apoptosis of tumor cells was detected by using LASB. We analysised gross tumor volume, survival of mice, and the proliferation of CTLs, as well as its specific lethal effect on tumor cells. Results: Low dose chemotherapy(5-Fu, DDP) can induce apoptosis of tumor cells. .Intratumoral administration of DC enhanced the effect of low dose chemotherapy(5-Fu, DDP),gross tumor volumes of both sides reduced obviously(P<0.05).it also increased the survival rate, proliferation and activation of CTLs, which reinforced the lethal effect on MFC(P,0.01). When the effector-to-target ratio were 40:1,20:1,10:1and 5:1,the killing and wounding rate after 72h averaged 87.64%,70.32%,34.63% and 13.87% respectively. It also can kill the MFC selectively(P<0.01). Conclusions: Low dose chemotherapy can induce the apoptosis of tumor cells. Combined biotherapy of DC and low dose chemotherapy can induce specific anti-tumor effect, which show a new way for DC's clinical usage.