# Glycosylation and Immune Evasion in Urologic Tumors

> **NIH NIH U01** · STANFORD UNIVERSITY · 2020 · $618,139

## Abstract

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.

## Key facts

- **NIH application ID:** 9908058
- **Project number:** 5U01CA226051-02
- **Recipient organization:** STANFORD UNIVERSITY
- **Principal Investigator:** JAMES D. BROOKS
- **Activity code:** U01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $618,139
- **Award type:** 5
- **Project period:** 2019-05-01 → 2024-04-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9908058

## Citation

> US National Institutes of Health, RePORTER application 9908058, Glycosylation and Immune Evasion in Urologic Tumors (5U01CA226051-02). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/9908058. Licensed CC0.

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