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Dr. Freeman received his PhD from Harvard University in 1979 and also joined DFCI that year. He did postdoctoral training in the laboratory of Dr. Harvey Cantor and then with Dr. Lee Nadler. Principally involved in basic laboratory research, he has studied the B7-CD28 gene family, showing that B7-2/CD28 is the major costimulatory pathway for T cell activation and that PD-L1/PD-1 is the major coinhibitory pathway for T cell activation.
About the Freeman Lab
The Freeman Laboratory studies the contribution of costimulatory signals to the immune response. Following the discovery of PD-L1 and PD-L2 as the ligands for the PD-1 receptor on T cells, we demonstrated the inhibitory function of PD-L1 and PD-L2 on T cells and showed that blockade of this pathway enhanced T cell activation, proliferation, and cytokine production. Further studies showed that PD-L1 is highly expressed by many solid tumors/hematological malignancies, and that blockade of PD-L1 enhances killing of PD-L1 positive targets by CD8 T cells. Recently, PD-1 blocking antibodies were approved by the FDA for the treatment of melanoma and lung cancer.
Our group also discovered the B7-1 and B7-2 molecules that bind to the costimulatory CD28 and coinhibitory CTLA-4 receptor and provide the critical costimulatory signal for full T cell activation, clonal expansion, and development of effector function through their interaction with CD28 on T cells. Following T cell activation, the B7-1–B7-2 interaction with CTLA-4, expressed on activated T cells, leads to down-regulation of T cell activation, whereas stimulation of the TCR alone leads to T cell clonal anergy. Thus, blockade of B7-1 and B7-2 can be used to establish antigen-specific tolerance for transplantation or the alleviation of autoimmunity.
Conversely, B7-1/B7-2 expression can stimulate an immune response, and the introduction of B7-1 or B7-2 into tumors can stimulate an anti-tumor response leading to tumor rejection and anti-tumor immunity. Recently, we have cloned two novel members of the B7 gene family, which bind to receptors expressed on activated T cells and further regulate the development of an immune response. Current studies focus on the function of these novel B7 genes and their interactions with the B7/CD28-CTLA-4 pathway.
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