T cell-encoded CD80 and 4-1BBL induce auto- and transcostimulation, resulting in potent tumor rejection

Nat Med. 2007 Dec;13(12):1440-9. doi: 10.1038/nm1676. Epub 2007 Nov 18.


To reject tumors, T cells must overcome poor tumor immunogenicity and an adverse tumor microenvironment. Providing agonistic costimulatory signals to tumor-infiltrating T cells to augment T cell function remains a challenge for the implementation of safe and effective immunotherapy. We hypothesized that T cells overexpressing selected costimulatory ligands could serve as cellular vehicles mediating powerful, yet constrained, anatomically targeted costimulation. Here, we show that primary human T cells expressing CD80 and 4-1BB ligand (4-1BBL) vigorously respond to tumor cells lacking costimulatory ligands and provoke potent rejection of large, systemic tumors in immunodeficient mice. In addition to showing costimulation of bystander T cells (transcostimulation), we show the effect of CD80 and 4-1BBL binding to their respective receptors in the immunological synapse of isolated single cells (autocostimulation). This new strategy of endowing T cells with constitutively expressed costimulatory ligands could be extended to other ligand-receptor pairs and used to enhance any targeted adoptive transfer therapy.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • 4-1BB Ligand / metabolism*
  • Adoptive Transfer
  • Animals
  • Antigen-Presenting Cells
  • B7-1 Antigen / metabolism*
  • Cell Line, Tumor
  • Humans
  • Immune System
  • Mice
  • Mice, SCID
  • Microscopy, Confocal
  • Neoplasms / immunology*
  • Neoplasms / metabolism
  • Protein Binding
  • Retroviridae / metabolism
  • T-Lymphocytes / metabolism


  • 4-1BB Ligand
  • B7-1 Antigen