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Glycosylation and Immune Evasion in Urologic Tumors

Award Number: U01CA226051
ORGANIZATION: NATIONAL CANCER INSTITUTE
OPDIV: NIH
AWARD CLASS: COOPERATIVE AGREEMENT
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)
PERIOD OF PERFORMANCE START DATE: 05/01/2019
PERIOD OF PERFORMANCE END DATE: 04/30/2026

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Glycosylation and Immune Evasion in Urologic Tumors - PROJECT SUMMARY/ABSTRACT The ability of tumor cells to evade the immune system is a well-known, yet poorly understood phenomenon in early cancer development. Despite promising immunotherapy strategies that have emerged from targeting these interactions, there is relatively little known about the complete repertoire of receptor-ligand interactions that contribute to immune evasion. We seek to understand how glycosylation, a well-established aberrant modification in cancer, aids cancer cells in evading the immune system. Identification of glycoproteins that modulate immune function could lead to new types of therpaies and could also serve as companion diagnostic biomarkers to guide patient selection of immunotherapies at an early time point in prostate cancer and clear cell renal cell carcinoma. First, because sialic acid is known to be overexpressed on the surface of cancer cells, we will use intact glycoproteomics methods developed in-house to enrich and identify sialoglycoproteins from cancerous and matched healthy tissues from patients. Quantitative comparative analyses will reveal changes in sialoglycoprotein expression and illuminate candidate ligands for sialic acid-binding proteins in the tumor microenvironment that potentially contribute to immune inactivation. Correlation of these glycoproteomic datasets with RNA-seq data focused on glycogene expression will bolster the assignment of specific glycoforms as cancer biomarkers. Second, using immunohistochemistry and CODEX methods, we will analyze expression levels of sialic acid-binding immunoglobulin-type lectin (Siglec) receptor proteins on tumor- resident immune cells and cross-correlate the findings with RNA-seq data as well as immune cell markers. We will also probe for the presence of ligands for various Siglec isoforms on tumor cell surfaces and obtain spatial information about their distribution on immune cells in intact tumor tissue. For any Siglecs identified as prominently displayed on immune cells in the tumor environment, we will develop cell-based assays to probe their contribution to tumor cell immunoreactivity. Third, we will perform a genome-wide screening using CRISPRi to identify genes that facilitate the binding of Siglecs to cancer cells. Finally, we will correlate the datasets from Aims 1, 2, and 3 with patient outcomes in a larger set of tissue samples contained on a tissue microarray, and evaluate their utility as prognostic indicators.


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 = $0 )
2025	2023	THE LELAND STANFORD JUNIOR UNIVERSITY	450 JANE STANFORD WAY	STANFORD	CA	94305	SANTA CLARA	USA	Cancer Detection and Diagnosis Research	000	5	5/6/2025	NON-COMPETING CONTINUATION	$0
														Subtotal = $0

Issue Date FY: 2024 ( Subtotal = $0 )
2024	2023	THE LELAND STANFORD JUNIOR UNIVERSITY	450 JANE STANFORD WAY	STANFORD	CA	94305	SANTA CLARA	USA	Cancer Detection and Diagnosis Research	000	5	6/7/2024	NON-COMPETING CONTINUATION	$0
														Subtotal = $0

Issue Date FY: 2023 ( Subtotal = $583,786 )
2023	2023	THE LELAND STANFORD JUNIOR UNIVERSITY	450 JANE STANFORD WAY	STANFORD	CA	94305	SANTA CLARA	USA	Cancer Detection and Diagnosis Research	002	5	5/23/2023	NON-COMPETING CONTINUATION	$583,786
2023	2022	LELAND STANFORD JUNIOR UNIVERSITY, THE	450 JANE STANFORD WAY	STANFORD	CA	94305	SANTA CLARA	USA	Cancer Detection and Diagnosis Research	001	4	1/20/2023	NON-COMPETING CONTINUATION	$0
2023	2020	LELAND STANFORD JUNIOR UNIVERSITY, THE	450 JANE STANFORD WAY	STANFORD	CA	94305	SANTA CLARA	USA	Cancer Detection and Diagnosis Research	000	2	10/13/2022	NON-COMPETING CONTINUATION	$0
														Subtotal = $583,786

Issue Date FY: 2022 ( Subtotal = $588,870 )
2022	2022	LELAND STANFORD JUNIOR UNIVERSITY, THE	450 JANE STANFORD WAY	STANFORD	CA	94305	SANTA CLARA	USA	Cancer Detection and Diagnosis Research	002	4	8/24/2022	NON-COMPETING CONTINUATION	$28,037
2022	2022	LELAND STANFORD JUNIOR UNIVERSITY, THE	450 JANE STANFORD WAY	STANFORD	CA	94305	SANTA CLARA	USA	Cancer Detection and Diagnosis Research	001	4	7/1/2022	NON-COMPETING CONTINUATION	$560,833
2022	2021	LELAND STANFORD JUNIOR UNIVERSITY, THE	450 JANE STANFORD WAY	STANFORD	CA	94305	SANTA CLARA	USA	Cancer Detection and Diagnosis Research	000	3	5/10/2022	NON-COMPETING CONTINUATION	$0
														Subtotal = $588,870

Issue Date FY: 2021 ( Subtotal = $582,341 )
2021	2021	LELAND STANFORD JUNIOR UNIVERSITY, THE	450 JANE STANFORD WAY	STANFORD	CA	94305	SANTA CLARA	USA	Cancer Detection and Diagnosis Research	000	3	4/16/2021	NON-COMPETING CONTINUATION	$582,341
														Subtotal = $582,341

Issue Date FY: 2020 ( Subtotal = $618,139 )
2020	2020	LELAND STANFORD JUNIOR UNIVERSITY, THE	450 JANE STANFORD WAY	STANFORD	CA	94305	SANTA CLARA	USA	Cancer Detection and Diagnosis Research	000	2	4/29/2020	NON-COMPETING CONTINUATION	$618,139
														Subtotal = $618,139

Issue Date FY: 2019 ( Subtotal = $621,878 )
2019	2019	LELAND STANFORD JUNIOR UNIVERSITY, THE	450 SERRA MALL	STANFORD	CA	94305	SANTA CLARA	USA	Cancer Detection and Diagnosis Research	000	1	4/5/2019	NEW	$621,878
														Subtotal = $621,878

Grand Total All Awards = $2,995,014

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Glycosylation and Immune Evasion in Urologic Tumors

Award Number: U01CA226051

ORGANIZATION: NATIONAL CANCER INSTITUTE

OPDIV: NIH

AWARD CLASS: COOPERATIVE AGREEMENT

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

PERIOD OF PERFORMANCE START DATE: 05/01/2019

PERIOD OF PERFORMANCE END DATE: 04/30/2026

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