The purpose of the Aging and Immune Restoration Lab is to understand the cellular and molecular mechanisms that drive declining immune function with age. The research goal is to identify therapeutic targets for the improvement of treatment outcomes for aging immune systems.
Dr. Lancaster and members of the AIR research team are investigating several ongoing projects that address key breakdown areas in the aged immune response.
Incorporation of newly generated T cells
The thymus is an organ dedicated to the generation of T cells, components of the immune system that are essential for effective immune responses. While the thymus is critical for establishing T cells in early life, it continues to output new T cell clones throughout life, though at decreased numbers. Coincidentally, it has been observed that individuals with continued thymus output later in life often have improved outcomes against infection and disease, though the reason for this correlation is unknown.
After leaving the thymus, newly generated T cells, known as recent thymic emigrants (RTEs), are still vetted before earning a place in the T cell pool, in a process that is still unclear. Our goal is to investigate the mechanisms driving RTE maturation, to better understand how newly generated T cell clones are incorporated and promote diversity of the T cell repertoire.
Lymph node stromal support of naive T cells
The immune response against novel pathogens relies on the cohort of naive T cells maintained in the T cell population. With age, the proportion of naive T cells declines dramatically, though the forces driving this change are unclear.
Structural cells, known as stroma, reside in the lymph nodes and are known to be important in maintaining naive T cell survival. The organization and composition of lymph node stroma changes with age, though the impact of these changes on naive T cell maintenance is not yet determined. Our goal is to understand the mechanisms driving altered organization and function of lymph node stroma, to identify means to improve naive T cell numbers with age.
Impaired germinal center production during elderly immunization
The complete activation of B cells is critical for their ability to elicit germinal centers, organized tissue areas within the lymph node that are dedicated to the production of high-affinity antibodies. Upon pathogen challenge or immunization, the elderly often demonstrate poor germinal center production, which leads to reduced antibody generation. Thus, the level of vaccine protection conferred by the aged immune system can be diminished.
Complete B cell activation is dependent on help from activated T cells. The ability of aged T cells to promote B cell activation is still controversial. Our goal is to visualize the dynamic interaction between T cells and B cells during germinal center initiation and progression, to determine the contribution of the aged environment to defective immune outcomes.
Immunosuppression by the tumor microenvironment
Immunotherapy has revolutionized cancer treatment by igniting the immune system's natural ability to clear tumor cells. However, patient outcomes for many forms of cancer have not improved, as these cancers have cultivated tumor-protective and highly immunosuppressive tumor microenvironments (TMEs). Namely, the tumor elicits signaling pathways that alter the function of nearby stroma and immune cells so that they can support the TME.
Our goal is to understand the dynamics among tumor cells, immune cells and tumor-associated stroma in regulating the immunosuppressive TME so that we can predict and improve the success of immunotherapeutic regimens. Our research team uses advanced microscopy of complex live TME models to determine the spatial and temporal kinetics governing immunotherapy and the TME response.