T cell-encoded CD80 and 4-1BBL induce auto- and transcostimulation, resulting in potent tumor rejection. Academic Article uri icon

Overview

abstract

  • 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 date

  • November 18, 2007

Research

keywords

  • 4-1BB Ligand
  • B7-1 Antigen
  • Neoplasms

Identity

Scopus Document Identifier

  • 36849021712

Digital Object Identifier (DOI)

  • 10.1038/nm1676

PubMed ID

  • 18026115

Additional Document Info

volume

  • 13

issue

  • 12