Study finds metabolic checkpoint PHGDH as potential target to modulate tumor-associated macrophages

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The study highlights the enzyme PHGDH as a metabolic checkpoint in tumor-associated macrophages (TAMs) and their effect on tumor growth. Targeting PHGDH may improve cancer treatment and clinical immunotherapies by modulating the immune system's response to cancer cells. TAMs are typically considered tumor-promoting, making them a potential therapeutic target for improving patient outcomes.

A study by a scientific team from the University of Vienna and the MedUni Vienna, recently published in the top-class journal Cellular & Molecular Immunology, has a promising result from tumor research: The enzyme phosphoglycerate dehydrogenase (PHDGH) acts as a metabolic checkpoint in the function of tumor-associated macrophages (TAMs) and thus on tumor growth. Targeting PHGDH to modulate the cancer-fighting immune system could be a new starting point in cancer treatment and improve the effectiveness of clinical immunotherapies.

Our immune system constantly fights emerging cancer cells that arise from mutations. This process is controlled, among other things, by different types of macrophages. Tumor-associated macrophages (TAMs) are among the most abundant immune cells in the tumor microenvironment. They come from tissue-resident immune cells circulating in the blood that penetrate the tumor and differentiate there in response to various messenger substances (cytokines) and growth factors. In most solid tumors, TAMs are paradoxically considered to be tumor-promoting (“protumorigenic”) overall: they promote tumor growth and metastasis by suppressing the immune response, promoting the vascular supply to the tumor and also increasing resistance to drug therapies – i.e. they generally correlate with a poor prognosis for the affected patients. Previous attempts to influence TAMs proved unsatisfactory because many patients had only a limited response to these therapeutic approaches. This underlines the urgency of finding new active ingredients and strategies.

Artificial intelligence and machine learning allow the precise diagnosis of metabolic markers and identification of checkpoints

Systems biologist and biochemist Wolfram Weckwerth from the Department

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