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Arachidonic acid metabolism, a cross point between "bad" and "good" macrophages in cancer: a novel therapeutic perspective?

Tumor-associated macrophages (TAMs) are one of the most abundant
population in the tumor microenvironment (TME). Several strategies have
been developed to deplete these cells. However, we and others have
proposed that their re-education towards a proinflammatory and tumoricidal
phenotype might be a more beneficial approach. Starting from our
observations that Hpgds expression is specific in TAMs and it is enhanced
in immunotherapy-resistant mouse and human tumors, we show that Hpgds
inhibition in melanoma-bearing mice strongly inhibits tumor growth and
imposes an anti-angiogenic, pro-inflammatory M1-like macrophage
phenotype. We propose to investigate the role of Hpgds, a key enzyme of
the arachidonic acid (AA) metabolism in TAMs, during tumor
progression, aiming to understand how the targeting of this synthetase
can re-educate TAMs toward an anti-tumoral M1-like phenotype by
shunting AA towards the production of anti-tumoral metabolites. The
ultimate goal of this project is to translate our finding in human
melanoma patients.

Date:1 Mar 2021 →  Today
Keywords:Arachidonic acid metabolism, macrophages, cancer
Disciplines:Cancer therapy