Abstract 1089: Characterization of the immune response to lymph mode metastases
Year: 2019
Type: conference-abstract
Abstract: Metastasis remains the principal cause of cancer mortality. Lymph nodes are the most common site of solid tumor metastases and lymph node status is the most significant prognostic indicator for patient outcome in human solid cancer. Although antitumor T cells are generated in lymph nodes, metastatic cancer cells are able to grow in this seemingly hostile microenvironment. Further, we recently found that lymph nodes are a portal for metastatic progression to distant organs. The challenge is how to treat cancer cells that have spread to lymph nodes or distant organs in order to prevent their growth and ideally eradicate them from the body. Most cancer therapies are developed against the primary tumor growing in its native microenvironment. Our previous work has shown 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. Here, our preliminary data show that cancer cells remodel the blood endothelium in metastatic lymph nodes. Although many blood vessels lack smooth muscle cell coverage, intravenous lectin perfusion reveals a functional blood vasculature within metastatic lymph nodes. However, we measured decreased expression of adhesion molecules on the vasculature in metastatic lymph nodes. Adoptive transfer of lymphocytes revealed impaired lymphocyte migration into mice harboring metastatic lymph nodes compared to naïve lymph nodes. Together, these findings suggest that decreased vascular adhesion molecule expression results in lymphocyte exclusion and impaired host immunosurveillance, leading to the progression of lymph node metastases. Our ongoing work seeks to inform therapeutic strategies that will enhance functional antitumor T cell infiltration into metastatic tumors and prevent their spread to distant organs.Citation Format: Dennis Jones, Timothy Padera. Characterization of the immune response to lymph mode metastases [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr 1089.
Source: Tumor Biology
Authors: Dennis Jones, Timothy Padera
Institutions: Boston University, Massachusetts General Hospital
Language: English
Subfield: Oncology
Field: Medicine
Domain: Health Sciences
Open Access status: gold
Estimated APC paid: $1,500
OpenAlex ID: W2956003277