The MHC class Ib protein ULBP1 is a nonredundant determinant of leukemia/lymphoma susceptibility to γδ T-cell cytotoxicity

• Autor(a) principal: Lança, Telma
• Data de Publicação: 2010
• Outros Autores: 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
• Tipo de documento: Artigo
• Idioma: eng
• Título da fonte: Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos)
• Texto Completo: http://hdl.handle.net/10400.21/12197
• topic: 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

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.