# Understanding the mechanisms of immune suppression in lymph node metastases

> **NIH NIH K22** · BOSTON UNIVERSITY MEDICAL CAMPUS · 2020 · $188,676

## Abstract

Project Summary/Abstract
Metastasis remains the principal cause of cancer mortality. While lymph node status is the most significant prognostic
indicator for patient outcome in human solid cancer, the lymph node is also the most common site of solid tumor
metastases. Although the consequences of lymph node metastases are debated, nodal metastases present an opportunity to
study immunosuppressive mechanisms found in metastatic disease. Several studies have demonstrated
immunosuppression of pre-metastatic LNs, although it is unclear if preconditioning is necessary for tumor growth.
However, it is not known how the LN, a pillar of immunity, responds during metastatic growth. I've found that that
classical sprouting angiogenesis (as observed in the primary tumor) does not occur in metastatic lymph nodes and is
therefore not necessary for metastatic outgrowth. These results offer an explanation as to why past and ongoing clinical
trials using anti-angiogenesis therapy have not fared as well as predicted in patients with metastasis. Instead, specialized
endothelium in metastatic lymph nodes is remodeled, preserving blood flow, but decreasing immune cell migration into
the lymph node. The work proposed here aims to build a biological understanding of lymph node metastases in order to
define the factors that drive disease progression and identify new therapeutic interventions to improve patient survival.
Based on preliminary findings, I will test the hypothesis that lymph node metastases compromise anti-tumor immunity.
For Aim 1, I will characterize the tumor-induced changes in the lymph node microenvironment that facilitate diminished
lymphocyte infiltration into tumor colonies in metastatic lymph nodes. I will also measure the ability of metastatic lymph
nodes to mount an immune response during growth of lymph node metastases. Aim 2 focuses on determining whether
physical contact or soluble factors from cancer cells cause dysfunctional endothelium in metastatic lymph nodes. In order
to overcome a major barrier for a successful anti-tumor immune response, Aim 3 seeks to identify molecules that will
enhance T cell infiltration into tumors through upregulation of adhesion molecules needed for attachment to endothelium,
and ultimately, entry into tumors. Overall, this study seeks to increase the number of anti-tumor T cells and restore their
function in lymph node metastases to improve local and systemic anti-tumor immunity for cancer eradication.
Collectively, these studies will contribute to understanding the progression of metastases in the lymph node and distant
organs and may lead to novel therapeutics that suppress metastatic growth. The experiments proposed will lay the
foundation towards my career goal of becoming an independent investigator and leader in cancer biology research.

## Key facts

- **NIH application ID:** 10003192
- **Project number:** 5K22CA230315-03
- **Recipient organization:** BOSTON UNIVERSITY MEDICAL CAMPUS
- **Principal Investigator:** Dennis Jones
- **Activity code:** K22 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $188,676
- **Award type:** 5
- **Project period:** 2018-09-30 → 2022-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10003192

## Citation

> US National Institutes of Health, RePORTER application 10003192, Understanding the mechanisms of immune suppression in lymph node metastases (5K22CA230315-03). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10003192. Licensed CC0.

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