‘Bad fat’ suppresses killer T cells from attacking cancer

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Sumary of ‘Bad fat’ suppresses killer T cells from attacking cancer:

  • Salk researchers led by Professor Susan Kaech have found that the environment inside tumors (the tumor microenvironment) contains an abundance of oxidized fat molecules, which, when ingested by the killer T cells, suppresses their ability to kill cancer cells..
  • In a vicious cycle, those T cells, in need of energy, increase the level of a cellular fat transporter, CD36, that unfortunately saturates them with even more oxidized fat and further curtails their anti-tumor functions..
  • The discovery, published online in Immunity on June 7, 2021, suggests new pathways for safeguarding the immune system’s ability to fight cancer by reducing the oxidative lipid damage in killer T cells..
  • “Our findings uncovered a novel mode of immunosuppression in tumors involving the import of oxidized fats (AKA lipids) in T cells via the cellular fat transporter CD36, which impairs their anti-tumor functions locally.”.
  • They then observed how killer T cells respond to the oxidized LDLs in tumors and found that killer T cells adapted to the tumor microenvironment by increasing CD36 on their surface and ingesting an abundance of oxidized lipids..
  • Working with Brinda Emu’s lab at Yale University, they found this process served as a catalyst to drive even greater amounts of lipid oxidation internally in the killer T cells and ultimately repressed their defenses..
  • They confirmed that CD36 promoted T cell dysfunction in tumors by increasing oxidized lipid import, which caused greater lipid oxidation and damage within the T cells and triggered the activation of a stress response protein, p38..
  • “We found that when the T cells get ‘stressed out’ by oxidized lipids, they shut down their anti-tumor functions,”…

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