Wednesday, September 17, 2025 9/17/2025

Tryptophan-derived oncometabolites as novel mediators of cancer immune evasion

Award Number: F30CA294650
ORGANIZATION: NATIONAL CANCER INSTITUTE
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: FELLOWSHIP/SCHOLARSHIP/STUDENT LOANS
PERIOD OF PERFORMANCE START DATE: 07/28/2025
PERIOD OF PERFORMANCE END DATE: 07/27/2029

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Tryptophan-derived oncometabolites as novel mediators of cancer immune evasion - PROJECT SUMMARY Liver cancer incidence is rising globally, with an overall survival rate of about 20%. Developing new therapeutic strategies is therefore critical to improve treatment response and increase survival. Our lab has identified a novel metabolic vulnerability in liver cancer which could pave the way for new mechanisms of therapy. Starving tumors of the essential amino acid tryptophan (Trp) completely abrogates liver cancer growth in genetically engineered mouse models as well as syngeneic xenografts. Importantly, the vast majority of bodily Trp is metabolized and not used for protein synthesis. Therefore, we broadly tested adding back various Trp metabolites to identify those that were critical for tumor growth. We discovered that the novel oncometabolite indole-3-pyruvate (I3P) is the only downstream product of Trp capable of rescuing liver cancer growth. However, the growth-promoting effects of I3P are significantly stronger in vivo than in vitro, suggesting that it has a non cell-autonomous mechanism of action. I surveyed multiple different immune cell types relevant to the liver cancer microenvironment and found that I3P may play a critical role in modulating macrophage polarization. My studies will therefore focus on defining the role of I3P-mediated macrophage phenotypes in the immune response to liver cancer.


Issue Date FY	Funding FY	Legal Entity Name	Legal Entity Address	Legal Entity City	Legal Entity State	Legal Entity Zip Code	Legal Entity COUNTY	Legal Entity COUNTRY	Assistance Listing	Award Code	Budget Year	Action Date	Action Type	Action Amount

Issue Date FY: 2025 ( Subtotal = $40,872 )
2025	2025	THE UNIVERSITY OF TEXAS SOUTHWESTERN MEDICAL CENTER	5323 HARRY HINES BLVD	DALLAS	TX	75390	DALLAS	USA	Cancer Research Manpower	000	1	7/21/2025	NEW	$40,872
2025	2025	THE UNIVERSITY OF TEXAS SOUTHWESTERN MEDICAL CENTER	5323 HARRY HINES BLVD	DALLAS	TX	75390	DALLAS	USA	Cancer Research Manpower	001	1	7/21/2025	NEW	$0
														Subtotal = $40,872

Grand Total All Awards = $40,872

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Tryptophan-derived oncometabolites as novel mediators of cancer immune evasion

Award Number: F30CA294650

ORGANIZATION: NATIONAL CANCER INSTITUTE

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

AWARD ACTIVITY TYPE: FELLOWSHIP/SCHOLARSHIP/STUDENT LOANS

PERIOD OF PERFORMANCE START DATE: 07/28/2025

PERIOD OF PERFORMANCE END DATE: 07/27/2029

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