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Browsing by Author "Moita, Catarina F."

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  • The MHC class Ib protein ULBP1 is a nonredundant determinant of leukemia/lymphoma susceptibility to γδ T-cell cytotoxicity
    Publication . Lança, Telma; Correia, Daniel V.; Moita, Catarina F.; Raquel, Helena; Neves-Costa, Ana; Ferreira, Cristina; Ramalho, José S.; Barata, João T.; Moita, Luís F.; Gomes, Anita Q.; Silva-Santos, Bruno
    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.
    2010-03Journal article Open access Show more