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

T. Lança, D.V. Correia, C.F. Moita, H. Raquel, A. Neves-Costa, C. Ferreira, J.S. Ramalho, J.T. Barata, L.F. Moita, A.Q. Gomes, B. Silva-Santos

Research output: Contribution to journalArticle

74 Citations (Scopus)

Abstract

On the path to successful immunotherapy of hematopoietic tumors, γδ 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 γδ T cells remain unclear. Here we show that the expression levels of UL16-binding protein 1 (ULBP1) determine lymphoma susceptibility to γδ T cell-mediated cytolysis. Consistent with this, blockade of NKG2D, the receptor for ULBP1 expressed on all Vγ9+ 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 γδ 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 γδ T cell-based immunotherapy, and therefore propose ULBP1 to be used as a leukemia/lymphoma biomarker in upcoming clinical trials. © 2010 by The American Society of Hematology.
Original languageEnglish
Pages (from-to)2407-2411
Number of pages5
JournalBlood
Volume115
Issue number12
DOIs
Publication statusPublished - 2010

Keywords

  • major histocompatibility antigen class 1
  • natural killer cell receptor NKG2D
  • protein ulbp1
  • unclassified drug
  • lymphocyte antigen receptor
  • membrane protein
  • signal peptide
  • small interfering RNA
  • tumor marker
  • ULBP1 protein, human
  • article
  • cancer susceptibility
  • cell killing
  • controlled study
  • cytolysis
  • cytotoxic T lymphocyte
  • gene expression
  • human
  • human cell
  • leukemia
  • loss of function mutation
  • lymphoma
  • molecular recognition
  • nucleotide sequence
  • peripheral blood mononuclear cell
  • priority journal
  • protein function
  • risk factor
  • T lymphocyte
  • tumor biopsy
  • acute lymphoblastic leukemia
  • B cell leukemia
  • biopsy
  • clinical trial
  • genetics
  • immunology
  • immunotherapy
  • metabolism
  • methodology
  • pathology
  • T cell leukemia
  • tumor cell line
  • Biopsy
  • Cell Line, Tumor
  • Clinical Trials as Topic
  • Humans
  • Immunotherapy
  • Intracellular Signaling Peptides and Proteins
  • Leukemia, B-Cell
  • Leukemia, T-Cell
  • Lymphoma
  • Membrane Proteins
  • Precursor Cell Lymphoblastic Leukemia-Lymphoma
  • Receptors, Antigen, T-Cell, gamma-delta
  • RNA, Small Interfering
  • T-Lymphocytes, Cytotoxic
  • Tumor Markers, Biological

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