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Reposted by Katrin Böttcher

Nature @nature.com · 5d

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

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Katrin Böttcher @kboettcherlab.bsky.social · Jun 23

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

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...

www.journal-of-hepatology.eu

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Katrin Böttcher @kboettcherlab.bsky.social · Jun 23

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

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Katrin Böttcher @kboettcherlab.bsky.social · Jun 23

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

1

Katrin Böttcher @kboettcherlab.bsky.social · Jun 23

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.

1

Katrin Böttcher @kboettcherlab.bsky.social · Jun 23

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.

1

Katrin Böttcher @kboettcherlab.bsky.social · Jun 23

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

1

Katrin Böttcher @kboettcherlab.bsky.social · Jun 23

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.

1

Katrin Böttcher @kboettcherlab.bsky.social · Jun 23

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

Katrin Böttcher @kboettcherlab.bsky.social · Jun 23

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.

1

Katrin Böttcher @kboettcherlab.bsky.social · Jun 23

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)

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Katrin Böttcher @kboettcherlab.bsky.social · Jun 23

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

Katrin Böttcher @kboettcherlab.bsky.social · Jun 23

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.

1

Katrin Böttcher @kboettcherlab.bsky.social · Jun 23

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.

1

Katrin Böttcher @kboettcherlab.bsky.social · Jun 23

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

1

Katrin Böttcher @kboettcherlab.bsky.social · Jun 23

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.

1

Katrin Böttcher @kboettcherlab.bsky.social · Jun 23

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

Katrin Böttcher @kboettcherlab.bsky.social · Jun 23

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.

1

Katrin Böttcher @kboettcherlab.bsky.social · Jun 23

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

Katrin Böttcher @kboettcherlab.bsky.social · Jun 23

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

1

Katrin Böttcher @kboettcherlab.bsky.social · Jun 23

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.

1

Katrin Böttcher @kboettcherlab.bsky.social · Jun 23

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.

1

Katrin Böttcher @kboettcherlab.bsky.social · Jun 23

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

1

Katrin Böttcher @kboettcherlab.bsky.social · Jun 23

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.

1

Katrin Böttcher @kboettcherlab.bsky.social · Jun 23

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