The effect of PHD inhibitor on tumor microenvironment and tumor immune response.

Abstract

Since the approval of PHD inhibitors, PHD inhibitors have been used clinically, and many studies and clinical case reports have been reported in Japan. A lot of information has been accumulated on clinical usage. However, PHD inhibitors require careful administration for cancer patients due to their action mechanism through upregulate hypoxia-inducible factors (HIFs) level. In cancer cells, HIFs affect to tumor progression and contribute to chemo- and radio- resistance. On the other hand, upregulation of HIFs in immune cells is associated with inflammation and affected to suppress tumor progression. Although these controversial effects are not clear in vivo model. It is needed to reveal whether upregulating HIFs level is beneficial for cancer therapy or not. We have previously reported that PHD inhibitor treatment in tumor bearing mice model led to reconstitute tumor blood vessels and inhibit tumor growth. In addition, these phenomena caused of tumor infiltrated macrophages and altered these phenotypes. In this session, we will describe our findings on the mechanism of tumor growth suppression by PHD inhibitors. We will also discuss about the risks and benefits of PHD inhibitors.