Interrogating the Impact of B Cells and Tertiary Lymphoid Structures in Melanoma Brain Metastases
Abstract
Recent advances in melanoma have helped patients lead longer and healthier lives; however, there is an unmet need to improve therapeutic options, particularly for individuals who progress to metastatic disease. Our immune systems are internal barometers for the primary response to foreign invaders like virus and bacteria within our body. Despite cancer arising from irregular growth of our own cells, the immune system can effectively kill cancer cells just as it identifies and kills viral and bacterial infections. However, cancer can also effectively hide from the immune response (known as immune evasion), specifically because it grows from our normal cells becoming mutated or unchecked. Thus, preventing immune evasion and augmenting the immune response are now the focus of new and promising treatments. Immunotherapy is a promising cancer therapy which mobilizes our internal immune response to kill cancer. The three major immune players in cancer can be classified by function: helpers, killers, and suppressors. Helpers educate the killers. Killers directly attack and eliminate the cancer cells. Suppressors hinder the immune response and promote cancer growth. Current immune-based therapies target the killers; however, there are many other important immune components within cancer. Recently, the presence of another type of helper immune cell, the B cell, was also shown to be associated with better response to treatment. B cells can form cell clusters referred to as tertiary lymphoid structures (TLS) that function to locally educate other helpers and killers of the immune response. Further, the presence of these immune structures (TLS) in cancer correlates with better outcomes for patients. So far, much of the research regarding the role of the immune system in melanoma has focused on sites outside the brain such as the skin and lymph nodes. However, a good proportion of patients with advanced disease develop melanoma that spreads to the brain (melanoma brain metastases, MBM). MBM patients often have a shorter survival window; thus, new therapeutic targets are necessary for this vulnerable patient population. The goal of this proposal is to quantify B cells and examine if B cells can form immune structures (TLS) in MBM. We will use existing patient samples to visually examine these immune structures (TLS) using state-of-the-art imaging techniques. We will determine if the amount of B cells and composition of the immune structures (TLS) in MBM impacts patient survival. The vision of the MRP is to prevent melanoma initiation and progression to promote earlier interventions to enhance mission readiness and diminish melanoma burden on Service Members, Veterans, and the American public. This Idea Award will help us develop new therapies surrounding B cells and TLS to synergize with the currently effective immune-based therapies in metastatic melanoma. Further, it will aim to develop a systemic biomarker for progression to MBM so that treatment options can be implemented earlier.
Document Details
- Document Type
- DoD Grant Award
- Publication Date
- Dec 28, 2022
- Source ID
- W81XWH2210694
Entities
People
- Tullia C. Bruno
Organizations
- United States Army
- University of Pittsburgh