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Advisor(s)
Abstract(s)
On the path to successful immunotherapy of hematopoietic tumors, gamma-delta T cells offer great promise because of their human leukocyte antigen (HLA)-unrestricted targeting of a wide variety of leukemias/lymphomas. However, the molecular mechanisms underlying lymphoma recognition by gamma-delta T cells remain unclear. Here we show that the expression levels of UL16-binding protein 1 (ULBP1) determine lymphoma susceptibility to gamma-delta T cell-mediated cytolysis. Consistent with this, blockade of NKG2D, the receptor for ULBP1 expressed on all Vgamma9(+) T cells, significantly inhibits lymphoma cell killing. Specific loss-of-function studies demonstrate that the role of ULBP1 is nonredundant, highlighting a thus far unique physiologic relevance for tumor recognition by gamma-delta T cells. Importantly, we observed a very wide spectrum of ULBP1 expression levels in primary biopsies obtained from lymphoma and leukemia patients. We suggest this will impact on the responsiveness to gamma-delta T cell-based immunotherapy, and therefore propose ULBP1 to be used as a leukemia/lymphoma biomarker in upcoming clinical trials.
Description
Keywords
Biomarkers, Tumor Biopsy Cell line, Tumor Clinical trials as topic GPI-Linked Proteins Humans Immunotherapy Intracellular signaling peptides and proteins Leukemia, B-cell Leukemia, T-cell Lymphoma Membrane proteins Precursor cell lymphoblastic leukemia-lymphoma RNA, Small interfering Receptors, Antigen T-Lymphocytes, Cytotoxic T-cell Gamma-delta
Citation
Lanca T, Correia DV, Moita CF, Raquel H, Neves-Costa A, Gomes AQ, et al. The MHC class Ib protein ULBP1 is a nonredundant determinant of leukemia/lymphoma susceptibility to γδ T-cell cytotoxicity. Blood. 2010;115(12):2407-11.
Publisher
American Society of Hematology