PHD阻害薬によるがん微小環境と腫瘍免疫への影響

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

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<p>The blood vessel is important tissue structures to deliver oxygen, nutrition and so on. An abnormal blood vessel formation is a common feature of tumor tissue that were characterized by hyper-permeability, irregular vascularization, immature vessels and intravasation. Therefore, tumor tissue is exposed to low oxygen nutrition depletion and low pH due to hypoperfusion and elevated interstitial pressure. These environments are one of the reasons for chemo- and radio-resistance. Previously, we reported that prolyl hydroxylase (PHD) inhibitor induced tumor blood vessel normalization and improved tumor microenvironment in tumor mouse model. However, effects of PHD inhibitor on tumor progression is controversial. Enhanced hypoxia inducible factors (HIFs) signaling in cancer cells act to promote cancer proliferation and metastases. On the other hand, increasing of HIFs signaling in immune cells may lead to activate inflammation and elicit anti-tumor effect. In this session, we will talk about our study how PHD inhibitor improved tumor microenvironment and focused on tumor infiltrate immune cells were phenotypic alteration after PHD inhibitor treatment in mouse model. We will also discuss about usefulness of PHD inhibitor for anti-cancer therapy.</p>

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