Katrin Böttcher

A photo of a Nobel medal

BREAKING: The Nobel Prize in Physiology or Medicine has been awarded jointly to Mary E. Brunkow, Fred Ramsdell, and Shimon Sakaguchi "for their discoveries concerning peripheral immune tolerance"

Stay tuned for more.
#NobelPrize

Polyunsaturated fatty acid-induced metabolic exhaustion and ferroptosis impair the anti-tumour function of MAIT cells in MASLD Mucosal-associated invariant T (MAIT) cells constitute a highly abundant innate-like T cell population in the human liver that is critical for immune surveillance of hepatic cancers but often dysfunct...

9/ 📖 Read more: www.journal-of-hepatology.eu/article/S016...

@easlnews.bsky.social @jhepatology.bsky.social @cd1mr1.bsky.social
#Immunometabolism #MAITcells #LiverImmunology #Ferroptosis #MASLD #HCC #LipidPeroxidation #TcellDysfunction #CancerImmunotherapy #TumorMicroenvironment #FattyLiver

8/ 🙏 Grateful to an outstanding team of collaborators and co-authors for their input to our project. @knollelab.bsky.social @jboettcherlab.bsky.social and all others that are not on social media

7/ 🏥 Clinical implications:
The PUFA–lipid peroxide axis we have identified represents a targetable metabolic checkpoint to enhance immunotherapy in HCC.

6/ 💡 Conclusion:
MASLD generates a lipid-driven immunosuppressive microenvironment by inducing metabolic exhaustion-mediated dysfunction and ferroptosis in MAIT cells - an abundant intrahepatic T cell subset with anti-tumour properties.

5/
• Interfering with lipid peroxide formation reverses MAIT dysfunction and restores anti-cancer activity.
• A PUFA-MAIT cell gene signature correlates with poor overall survival of patients with HCC.

4/
• PUFAs induce intracellular lipid peroxidation, driving metabolic exhaustion – i.e. mitochondrial and glycolytic dysfunction – and triggering ferroptosis.

3/ 🔬Core findings:
• In MASLD, MAIT cells exhibit profound functional exhaustion, including impaired cytokine production and anti-tumour activity.
• Mechanistically, PUFAs accumulate selectively in MAIT cells, not in conventional CD8⁺ or NK cells.

2/ In our study, we identify a previously unrecognised immunometabolic axis that links polyunsaturated fatty acids (PUFAs) to MAIT cell dysfunction in patients with MASLD.

1/ Our latest findings provide a possible mechanism on why patients with MASLD (metabolic dysfunction-associated steatotic liver disease) are more vulnerable to liver cancer.

I am more than happy that our study on MAIT cells in MASLD and their role in liver cancer immunity is now out in Journal of Hepatology!! 🤩
⬇️ Here's a thread about:
🧬 Immunometabolic dysfunction of MAIT cells in MASLD: A novel barrier to liver cancer immunity 🧬
(led by Sebastian Deschler)

7/ 💡 Clinical implications:
Targeting the PUFA–lipid peroxide axis represents a targetable metabolic checkpoint to enhance immunotherapy in HCC.

6/ 🧠 Conclusion:
MASLD generates a lipid-driven immunosuppressive microenvironment by inducing metabolic exhaustion-mediated dysfunction and ferroptosis in MAIT cells—an abundant intrahepatic T cell subset with anti-tumour properties.

5/
• Interfering with lipid peroxide formation reverses MAIT dysfunction and restores anti-cancer activity.
• A PUFA-MAIT cell gene signature correlates with poor overall survival of patients with HCC.

4/
• PUFAs induce intracellular lipid peroxidation, driving metabolic exhaustion – mitochondrial and glycolytic dysfunction – and triggering ferroptosis.

3/ 🔬Core findings:
• In MASLD, MAIT cells exhibit profound functional exhaustion, including impaired cytokine production and anti-tumor activity.
• Mechanistically, PUFAs accumulate selectively in MAIT cells, not in conventional CD8⁺ or NK cells.

2/ In our study, we identify a previously unrecognized immunometabolic axis that links polyunsaturated fatty acids (PUFAs) to MAIT cell dysfunction in patients with MASLD.

1/ Our latest findings provide a possible mechanism on why patients with MASLD (metabolic dysfunction-associated steatotic liver disease) are more vulnerable to liver cancer.

8/ 🙏 Grateful to an outstanding team of collaborators and co-authors for their input to our project. @knollelab.bsky.social @jboettcherlab.bsky.social

7/ 💡 Clinical implications:
Targeting the PUFA–lipid peroxide axis represents a targetable metabolic checkpoint to enhance immunotherapy in HCC.

6/ 🧠 Conclusion:
MASLD generates a lipid-driven immunosuppressive microenvironment by inducing metabolic exhaustion-mediated dysfunction and ferroptosis in MAIT cells—an abundant intrahepatic T cell subset with anti-tumour properties.

5/
• Interfering with lipid peroxide formation reverses MAIT dysfunction and restores anti-cancer activity.
• A PUFA-MAIT cell gene signature correlates with poor overall survival of patients with HCC.

4/
• PUFAs induce intracellular lipid peroxidation, driving metabolic exhaustion – mitochondrial and glycolytic dysfunction – and triggering ferroptosis.

3/ 🔬Core findings:
• In MASLD, MAIT cells exhibit profound functional exhaustion, including impaired cytokine production and anti-tumour activity.
• Mechanistically, PUFAs accumulate selectively in MAIT cells, not in conventional CD8⁺ or NK cells.

2/ In our study, we identify a previously unrecognised immunometabolic axis that links polyunsaturated fatty acids (PUFAs) to MAIT cell dysfunction in patients with MASLD.

1/ Our latest findings provide a possible mechanism on why patients with MASLD (metabolic dysfunction-associated steatotic liver disease) are more vulnerable to liver cancer.

The team is growing - if you’re interested in doing a PhD in translational research at the interface of #immunology, #oncology and #Tcellengineering at the M3 Research Center in Tübingen, follow the link below for more information and apply!

jobs.medizin.uni-tuebingen.de/Job/6357/PhD...

🤩 Thrilled and honoured to talk MAIT cells at the Falk Experimental Days of Hepatology among a fantastic lineup of researchers in Lyon today 🤩#MAITs #hepatology #translation #immunology

Watch this space, we’re moving! ⬇️

www.medizin.uni-tuebingen.de/de/das-klini...

#MAITcells #Tcells #CARTcells #liverimmunology #MR1 #cancer #immunometabolism #Tcellengineering #immunotherapy #immuneoncology