# Targeting lymph node metastases to prevent cancer progression

> **NIH NIH R01** · MASSACHUSETTS GENERAL HOSPITAL · 2022 · $69,448

## Abstract

This administrative supplement will support the completion of the current Aims of R01CA214913. Completing
the current Aims will also provide preliminary data to respond to the Summary Statement of the A0 renewal
application. These preliminary data will strengthen the A1 submission of the renewal application. Breakthroughs
in our knowledge of the molecular and cellular mechanisms regulating metastasis have yet to be broadly
translated into improved survival rates for patients with metastatic disease. Lymph node metastasis in a cancer
patient brings with it a poorer prognosis and the recommendation for systemic therapy. However, it is unclear
whether lymphatic metastases are only predictive or whether they play a role in cancer progression and the
emergence of distant metastases. Evidence shows that treating lymph node metastases improves survival in
some patients. The work proposed here aims to build a biological understanding of lymph node metastases in
order to define their role in disease progression and identify new therapeutic interventions to improve patient
survival. Recently, we have shown that lymph node metastases do not require angiogenesis to grow and do not
respond to anti-angiogenic therapy. We will build upon our unique expertise by addressing why lymph node
metastasis are such strong prognostic indicators and explore how lymph node metastasis drive cancer
progression. Specifically, we will test the hypotheses that lymph node metastases disseminate to distant sites
(Aim 1) and inhibit the ability of the immune system to develop and maintain anti-tumor immunity (Aim 2). We
will accomplish our goals using innovative animal models that allow state-of-the-art intravital microscopy of
spontaneous lymph node metastasis. In Aim 1, we will determine whether cancer cells utilize the fibroblastic
reticular cell-lined conduit system in lymph nodes to home to blood vessels and spread to distant sites. We will
attempt to block this process. In Aim 2, we will determine whether metastatic lymph nodes retain the ability to
initiate immune responses to new antigens. Further, we will determine the mechanism of immune suppression
in metastatic lymph nodes. We will attempt to increase immune effector function in lymph node metastases to
eradicate lymph node disease and stimulate systemic anti-tumor immunity. In completing these aims, we will
have better lymph node focused therapeutic options to limit the growth and spread of cancer from lymph nodes
and thus provide better outcomes for patients. Dr. Padera is an expert in intravital microscopy of the lymphatic
system and mechanisms of lymph node metastasis. Critical elements to achieving these goals are intravital
imaging equipment, complex animal models and functional immunological assays, all available in the PI’s
laboratory. In addition, the assembled team has complementary expertise that will enable them to overcome any
problems that occur during the project, uniquely positioning us to address these...

## Key facts

- **NIH application ID:** 10542290
- **Project number:** 3R01CA214913-05S1
- **Recipient organization:** MASSACHUSETTS GENERAL HOSPITAL
- **Principal Investigator:** TIMOTHY P PADERA
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $69,448
- **Award type:** 3
- **Project period:** 2017-03-02 → 2023-01-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10542290

## Citation

> US National Institutes of Health, RePORTER application 10542290, Targeting lymph node metastases to prevent cancer progression (3R01CA214913-05S1). Retrieved via AI Analytics 2026-05-28 from https://api.ai-analytics.org/grant/nih/10542290. Licensed CC0.

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