Role of urokinase-type plasminogen activator in local immunotherapy

We have previously reported that intratumoral injection of a mixture of OK-432 and fibrinogen (OK/fbg) is very effective for local immunotherapy of colorectal cancer, but has little influence on breast cancer, while addition of activated macrophages to OK/fbg (OK/fbg/mo) has a marked effect on breast cancer. In this study, we analyzed the role of urokinase-type plasminogen activator (uPA) in local immunotherapy. We found that uPA levels in breast cancer tissue were lower than in colorectal cancer tissue. Injection of OK-432 into breast cancers neither increased the uPA level nor caused tumor regression. Although OK/fbg injection caused an increase of uPA, tumor regression was restricted to the area around the injection site. With OK/fbg/mo however, uPA levels increased much more markedly and extensive tumor necrosis was observed in all cases. These findings suggest that uPA plays an important role in tumor regression during local immunotherapy.