Toll-like receptors in tumor immunotherapy.


Journal Article (Review)

Lymphodepletion with chemotherapeutic agents or total body irradiation (TBI) before adoptive transfer of tumor-specific T cells is a critical advancement in the treatment of patients with melanoma. More than 50% of patients that are refractory to other treatments experience an objective or curative response with this approach. Emerging data indicate that the key mechanisms underlying how TBI augments the functions of adoptively transferred T cells include (a) the depletion of regulatory T cells (T(reg)) and myeloid-derived suppressor cells that limit the function and proliferation of adoptively transferred cells; (b) the removal of immune cells that act as "sinks" for homeostatic cytokines, whose levels increase after lymphodepletion; and (c) the activation of the innate immune system via Toll-like receptor 4 signaling, which is engaged by microbial lipopolysaccharide that translocated across the radiation-injured gut. Here, we review these mechanisms and focus on the effect of Toll-like receptor agonists in adoptive immunotherapy. We also discuss alternate regimens to chemotherapy or TBI, which might be used to safely treat patients with advanced disease and promote tumor regression.

Full Text

Duke Authors

Cited Authors

  • Paulos, CM; Kaiser, A; Wrzesinski, C; Hinrichs, CS; Cassard, L; Boni, A; Muranski, P; Sanchez-Perez, L; Palmer, DC; Yu, Z; Antony, PA; Gattinoni, L; Rosenberg, SA; Restifo, NP

Published Date

  • September 15, 2007

Published In

Volume / Issue

  • 13 / 18 Pt 1

Start / End Page

  • 5280 - 5289

PubMed ID

  • 17875756

Pubmed Central ID

  • 17875756

International Standard Serial Number (ISSN)

  • 1078-0432

Digital Object Identifier (DOI)

  • 10.1158/1078-0432.CCR-07-1378


  • eng

Conference Location

  • United States