Our laboratory is a core laboratory in the MGH Brain Tumor Immunology and Immunotherapy Program. We are focused on understanding the immune response to brain tumors in the context of the unique anatomic context of the central nervous system (CNS).  Malignant brain tumors, such as glioblastoma (GBM), still do not have any FDA-approved immunotherapies, and we do not have a good understanding of how the immune response works in the central nervous system (CNS) especially in light of the site-specific features of the CNS.  We have therefore developed our program around the “brain tumor immunity cycle” in which we are dissecting the components of how immune responses may develop to progressing brain tumors using the intersection of preclinical models, the study of patient-derived tissues and cells, and the study of novel clinical trials/protocols to develop the following research areas:
Tumor antigen discovery: We are investigating the types of antigens that T cells may recognize during the endogenous response to GBM and other brain tumors.  We employ both preclinical models, in which we were the first to identify endogenous neoantigen immunogenicity, as well as translational approaches using ex vivo clinical specimens to study T cell specificity in our patients.
  
Antigen transit dynamics and presentation: We are studying the nature of antigen egress from the brain as well as the identity of the antigen presenting cells in CNS tumors.  We have already completed first-in-human studies to understand the transit of antigen in brain tumor settings.  Complementing this question, we have identified a particular dendritic cell subset that is required for antigen-specific responses to brain tumors and have used novel approaches to extend these findings to the human setting.  How brain tumor antigen is acquired, transferred, and presented remains a huge question in the field and is a major emphasis in the lab.  

Antigen/tumor targeting: We are exploring ways to target antigens that we identify both in preclinical as well as patient settings through novel personalized clinical trial programs.  We are actively studying novel vaccination and cell therapy approaches both to attack antigen-specific tumors and also to remodel the immune microenvironment.  

Meningeal immunobiology: We have become increasingly interested in the meningeal layers that surround the CNS, having described first single cell-level description of human dura and its immunological cell composition. We have identified key immune cells within the dural landscape and are exploring the functional contributions of this unique tissue site to brain tumor immune responses.