muirlab.bsky.social
https://themuirlab.org/
(Extra)Cellular Cancer Biology
@UChicagoCCB
56 posts
896 followers
810 following
Regular Contributor
Active Commenter
comment in response to
post
Awesome work!! Congratulations!
comment in response to
post
Very cool, congratulations!
comment in response to
post
Very cool! Congrats!!
comment in response to
post
Super exciting work! Congratulations!
comment in response to
post
Yes, great turn out and super dynamic Q/A! Thanks for coming and sharing your work and thoughts on stromal metabolism!
comment in response to
post
Thanks Issam!!
comment in response to
post
Big thank you to the Cancer Research Foundation and the Brinson Foundation for supporting this work in our lab! 14/
comment in response to
post
Super to work with Greg, Drew and Jeremy @delgoffelab.bsky.social and Hardik Shah at the UCCCC Metabolomics facility. Everything that most people get into science for. Exciting new tools, getting to work across boundaries with super smart folks on problems whose solutions will save lives. 13/
comment in response to
post
(3) Phosphoethanolamine causes heritable dysfunction. How? Related to how PE metabolism regulated Tfh differentiation (pubmed.ncbi.nlm.nih.gov/34234346/)? Or senescence (pubmed.ncbi.nlm.nih.gov/38409325/)? 12/
comment in response to
post
A lot of questions to follow: (1) How do tumors accumulate phosphoethanolamine? (2) How do T cells take up phosphoethanolamine? Seems like specific transport as T cells do not take up related metabolites, but no know transporter. Can we target these processes to improve immunotherapy? 11/
comment in response to
post
If we engineered mouse tumors to secrete less phoshoethanolamine in the TME, we found better TCR signaling in TILs and tumor control. So, phosphoethanolamine is a critical barrier to TIL function in vivo. 10/
comment in response to
post
We found phosphoethanolamine suppresses levels of diacylglycerol, a key second messenger, in T cells and limits TCR signal transduction. 9/
comment in response to
post
First arginine depletion limits T cell growth. That squares with many past reports. But also phosphoethanolamine? Weird one for us. This Kennedy pathway intermediate accumulates in many cancers (including every one we looked at). But has not been connected to immune function in cancer before. 8/
comment in response to
post
Nice thing about TIFM is that it is chemically defined. So can drill down and find the metabolic stresses causing T cell dysfunction. What are they? Drum roll… 7/
comment in response to
post
We found T cells in TIFM were quite dysfunctional. This strongly suggests that pathophysiology levels of nutrients in the TME are a key barrier to T cell function in tumors. 6/
comment in response to
post
We were super fortunate to team up with @delgoffelab.bsky.social to see how these media impacted T cell function and biology. 5/
comment in response to
post
We previously quantified metabolite levels in the TME (elifesciences.org/articles/44235) and built custom chemically defined media (Tumor Interstitial Fluid Medium TIFM) that contain TME levels of nutrients (elifesciences.org/articles/81289). 4/
comment in response to
post
Metabolism is critical for T cell function, so we set out to determine if pathophysiological levels of nutrients in tumors cause TIL dysfunction. Is metabolism acting as a barrier independent of other checkpoints? 3/
comment in response to
post
Tumor infiltrating lymphocytes (TILs) become rapidly dysfunctional in many solid cancers which limits immunotherapeutic efficacy for patients. Why? 2/
comment in response to
post
Congrats!
comment in response to
post
Super cool work!!