Thursday, December 18, 2025 12/18/2025

S100A4 mediated immune suppression in GBM

Award Number: R01NS121405
ORGANIZATION: NATIONAL INSTITUTE OF NEUROLOGICAL DISORDERS AND STROKE
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)
PERIOD OF PERFORMANCE START DATE: 04/01/2021
PERIOD OF PERFORMANCE END DATE: 01/31/2026

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S100A4 mediated immune suppression in GBM - Project Summary Glioblastoma (GBM) is the most common and aggressive malignant brain tumor in adults and is virtually incurable. Despite aggressive treatments that include surgery, radiation therapy, and chemotherapy, the average survival is 15.4 months, with less than 5% of patients surviving > 5 years. Immunotherapy is a promising new approach to treat GBM as it harnesses one’s own immune system to recognize and kill aberrant cancer cells. Unfortunately, ongoing trials with immunotherapies show disappointing results in most GBM patients, indicating that we need to better understand the intricate and dynamic interactions between glioma and immune cells that generate and maintain highly immune suppressive microenvironment in GBM. The major goal of this application is to test our hypothesis that S100A4 is a critical regulator of the GBM immune landscape. S100A4 is a small calcium binding protein that functions intracellularly as well as extracellularly. We recently reported that S100A4 is necessary for human and mouse glioma stem cell self- renewal. Our single cell RNA-sequencing analyses of human GBM shows that S100A4 is expressed in both glioma cells and immune suppressive leukocytes. Consistently, TCGA data analyses indicate that S100A4 expression is strongly correlated with primary and recurrent GBM patient survival, the mesenchymal subtype, and immune-suppressive macrophage markers (such as CD163, CD206, and IL10). Importantly, our unpublished results show that S100A4 in human and mouse glioma cells regulates expression of chemokines and cytokines that control immune cell infiltration and polarization towards immune suppressive phenotypes. Notably, knocking down S100a4 in glioma cells is sufficient to reprogram the immune environment and allow dramatic increase in T-cell infiltration and activation in mouse gliomas. Furthermore, deletion of S100a4 in the host mouse is also sufficient to reprogram the glioma immune landscape and extend survival (manuscripts in preparation). Therefore, we hypothesize that S100A4 functions in both glioma and immune to promote immune-suppressive environment in GBM through multiple mechanisms. To test this hypothesis, we will: 1) elucidate mechanisms through which S100A4 expression in glioma cells promotes local immune-suppressive microenvironment in GBM (Aim 1); and 2) determine mechanisms through which S100a4 expression in immune cells controls myeloid and T cell trafficking, polarization, and function (Aim2). Successful completion of this study will reveal how S100A4 regulates glioma associated immune cell infiltration/polarization and identify a potential novel immunotherapy target to treat GBM.


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: 2026 ( Subtotal = $0 )
2026	2025	THE METHODIST HOSPITAL RESEARCH INSTITUTE	6565 FANNIN ST STE D200	HOUSTON	TX	77030	HARRIS	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	000	5	12/11/2025	NON-COMPETING CONTINUATION	$0
														Subtotal = $0

Issue Date FY: 2025 ( Subtotal = $394,788 )
2025	2025	METHODIST HOSPITAL, THE	6670 BERTNER AVE	HOUSTON	TX	77030	HARRIS	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	000	5	2/14/2025	NON-COMPETING CONTINUATION	$394,788
														Subtotal = $394,788

Issue Date FY: 2024 ( Subtotal = $425,493 )
2024	2024	METHODIST HOSPITAL, THE	6670 BERTNER AVE	HOUSTON	TX	77030	HARRIS	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	001	4	5/3/2024	NON-COMPETING CONTINUATION	$30,705
2024	2024	METHODIST HOSPITAL, THE	6670 BERTNER AVE	HOUSTON	TX	77030	HARRIS	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	000	4	1/24/2024	NON-COMPETING CONTINUATION	$394,788
														Subtotal = $425,493

Issue Date FY: 2023 ( Subtotal = $438,652 )
2023	2023	METHODIST HOSPITAL, THE	6670 BERTNER AVE	HOUSTON	TX	77030	HARRIS	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	000	3	2/21/2023	NON-COMPETING CONTINUATION	$438,652
														Subtotal = $438,652

Issue Date FY: 2022 ( Subtotal = $438,652 )
2022	2022	METHODIST HOSPITAL, THE	6670 BERTNER AVE	HOUSTON	TX	77030	HARRIS	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	000	2	1/26/2022	NON-COMPETING CONTINUATION	$394,788
2022	2022	METHODIST HOSPITAL, THE	6670 BERTNER AVE	HOUSTON	TX	77030	HARRIS	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	001	2	4/12/2022	NON-COMPETING CONTINUATION	$43,864
														Subtotal = $438,652

Issue Date FY: 2021 ( Subtotal = $465,405 )
2021	2021	METHODIST HOSPITAL, THE	6670 BERTNER AVE	HOUSTON	TX	77030	HARRIS	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	000	1	3/27/2021	NEW	$465,405
														Subtotal = $465,405

Grand Total All Awards = $2,162,990

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S100A4 mediated immune suppression in GBM

Award Number: R01NS121405

ORGANIZATION: NATIONAL INSTITUTE OF NEUROLOGICAL DISORDERS AND STROKE

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)

PERIOD OF PERFORMANCE START DATE: 04/01/2021

PERIOD OF PERFORMANCE END DATE: 01/31/2026

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