A new study by researchers from Sun Yat sen University and Zhejiang Cancer Hospital, published in Cancer Biology & Medicine reveals a surprising role for the metabolic enzyme PHGDH in breast cancer immunity. While traditionally linked to serine biosynthesis, PHGDH was found to relocate to the nucleus of macrophages, where it suppresses genes involved in glutamine metabolism by interacting with the transcription factor STAT3. This action shifts macrophages from a tumor promoting M2 like state to a tumor fighting M1 like phenotype.

The study showed that PHGDH expression is reduced in tumor associated macrophages, leading to weakened immune activation. Restoring PHGDH reversed this, enhancing anti tumor responses and slowing tumor growth in mouse models. The research highlights nuclear PHGDH as a key regulator of immune cell behavior and suggests it could be targeted to reshape the tumor microenvironment and improve immunotherapy outcomes. PHGDH may also serve as a biomarker to guide treatment strategies in breast cancer.

Source: https://www.news-medical.net/news/20250707/Metabolic-enzyme-PHGDH-found-to-play-a-surprising-role-in-breast-cancer-immunity.aspx