# Tumor and Immune Programming of Tumor-Associated  Endothelium

> **NIH NIH R01** · PALO ALTO VETERANS INSTIT FOR RESEARCH · 2020 · $439,634

## Abstract

PROJECT SUMMARY/ABSTRACT
 Blood vascular endothelial cells (BEC) control tumor growth through angiogenesis and differentiation of
support vessels, and direct the host immune response to cancer by regulating immune cell recruitment from
the blood. Recent studies emphasize the importance of specialized subsets of BEC in tumor biology, including
high endothelial venules (HEV, vessels specialized for lymphocyte recruitment) which help direct effective
tumor immunity. In spite of their central role in tumor biology, little is known about the BEC at the molecular
level, mechanisms that regulate tumor angiogenesis are poorly understood, and the precursors that give rise to
angiogenic tumor EC and to tumor-associated leukocyte-recruiting vessels remain to be determined.
 Under Aim 1 we will apply state-of-the-art single cell high dimensional mass label (CyTOF) flow cytometry
and single cell RNAseq analyses to uncover the diversity of EC subsets in tumors and their environment,
define the kinetics and subset-specificity of proliferative responses during tumor angiogenesis, and monitor the
emergence and maturation of functional HEV and other post capillary venules (PCV) for immune cell traffic.
Trajectory analyses will reveal developmental relationships of identified subsets including candidate
progenitors, and immunofluorescence histology and confocal tissue imaging will define their location within the
tumor and associated vasculature. Single cell BEC signatures will be mapped to the tumor vasculature using
quantitative tissue immunohistology. Under Aim 2, innovative fate mapping approaches will elucidate
precursor-product relationships among BEC subsets and will define clonal contributions of precursors to
angiogenic tumor EC, to specialized EC of support vessels, and to high endothelium. Aim 3 will mine
transcriptional profiles of induced EC subsets and apply pan-EC and EC subset-specific inducible gene
targeting systems to define pathways and mechanisms that control progenitor cell and amplifying tumor EC
activation, and that direct the differentiation of tumor-associated HEV. Novel bioinformatics tools will be applied
to uncover transcriptional programs and pathways that induce recruiting vessels in settings of immunotherapy.
 Generation of a comprehensive atlas of blood endothelial cell subsets, molecular phenotypes and
responses to tumorigenesis will open up new areas of investigation in cancer biology and immunology.
Elucidation of the mechanisms of endothelial cell specialization and homeostasis, including mechanisms
regulating endothelial cells that control lymphocyte traffic into tumors, may lead to novel targets and
approaches to enhance cancer immunotherapies.

## Key facts

- **NIH application ID:** 9832671
- **Project number:** 5R01CA228019-02
- **Recipient organization:** PALO ALTO VETERANS INSTIT FOR RESEARCH
- **Principal Investigator:** EUGENE C BUTCHER
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $439,634
- **Award type:** 5
- **Project period:** 2018-12-06 → 2023-11-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9832671

## Citation

> US National Institutes of Health, RePORTER application 9832671, Tumor and Immune Programming of Tumor-Associated  Endothelium (5R01CA228019-02). Retrieved via AI Analytics 2026-05-21 from https://api.ai-analytics.org/grant/nih/9832671. Licensed CC0.

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