Role of the Tumor-Immune Interplay in Breast Cancer Metastasis
Abstract
More than 150,000 women in the United States are living with a diagnosis of metastatic breast cancer (BCa). Nearly 41,000 deaths from BCa occur annually, virtually all due to metastatic disease, which remains the biggest hurdle for curing BCa. Therefore, a deeper understanding of the metastasis biology is key to developing better treatment strategies and achieving long-lasting therapeutic efficacies against BCa. While most studies so far have been focused on the genomic alterations of cancer cells that determine metastatic traits and their evolution during cancer progression, the exact roles of the host microenvironmental factors in driving the metastatic process remain largely unknown. Indeed, the non-transformed stroma cells within the primary tumors are believed to coevolve with tumor evolution and reshape the metastatic properties of tumor cells. Clinical and experimental studies suggest that infiltration of leukocytes such as macrophages into neoplastic mammary tissues can promote the development and invasion of BCa. Therefore, the identification of metastasis-promoting factors or mediators in the non-cancerous compartment will provide novel therapeutic targets for treating metastatic breast cancer. This application is built on our discovery that scavenger receptor A (SRA), an immune receptor that is abundantly expressed on BCa-associated macrophages but not on cancer cells, exhibits a previously unreported tumor-promoting feature, particularly in the metastatic process of BCa. The proposed studies aim to understand how this gene facilitates BCa growth and increases its invasiveness using multiple experimental models and approaches. Using preclinical models, we will evaluate our recently developed antibodies against this receptor for potential immunotherapy of BCa metastasis. It is anticipated that this successfully tested immunotherapy can be used in the adjuvant setting either alone or in combination with currently approved systemic treatments (e.g., hormonal therapy, chemotherapy) in patients who are at risk for developing metastasis. Given the previously established role of SRA as a suppressor of antitumor immunity, therapeutic blockade of this receptor may also be exploited to enhance or unleash the immune functions for elimination of established BCa metastases.
Document Details
- Document Type
- DoD Grant Award
- Publication Date
- Dec 05, 2021
- Source ID
- W81XWH2110056
Entities
People
- Xiang-Yang Wang
Organizations
- United States Army
- Virginia Commonwealth University