Irradiation enhances dendritic cell potential antitumor activity by inducing tumor cell expressing TNF-α

Dendritic cells (DCs)-based tumor vaccines have shown to be the promising methods for inducing therapeutic antitumor response. However, DCs alone rarely carry curative antitumor activity, and the immunosuppressive microenvironment may contribute to this defect of DC vaccinal function. Irradiation in combination with DCs has been shown to promote immune-mediated tumor destruction in preclinical studies. However, little is known about how irradiation alters the tumor microenvironment, and what host pathways modulate the activity of administrated DCs. In this study, BALB/c mice and the 4T1 breast cancer cell line were used in a tumor-bearing model. The tumor-bearing mice were irradiated locally up to 10 Gy for 3 consecutive days or a single dose of 30 Gy using a cesium source. Studies of dynamic change of the tumor microenvironment in irradiated versus untreated tumors revealed that there was no obvious change on IL-10, IL-6 and TGF-β expression or production, whereas increased TNF-α level within the first 2 weeks of irradiation. The increased TNF-α level is exactly right timing window for DCs injection, corresponding to the significant elevation of intratumoral CD8⁺ T infiltration and the regression of tumor size. With attention to scheduling, combination X-ray with DCs i.t. injection may offer a practical strategy to improve treatment outcomes.