Tumor necrosis factor is dispensable for the success of immunogenic anticancer chemotherapy

Yuting Ma, Takahiro Yamazaki, Heng Yang, Oliver Kepp, Lorenzo Galluzzi, Laurence Zitvogel, Mark J. Smyth, Guido Kroemer

Research output: Contribution to journalArticlepeer-review

22 Scopus citations

Abstract

The antineoplastic effects of anthracyclines have been shown to rely, at least in part, on a local immune response that involves dendritic cells (DCs) and several distinct subsets of T lymphocytes. Here, we show that the administration of anthracyclines to mice bearing established neoplasms stimulates the intratumoral secretion of tumor necrosis factor a (TNF α). However, blocking the TNF α/TNF receptor (TNFR) system by three different strategies-namely, (1) neutralizing antibodies, (2) etanercept, a recombinant protein in which TNFR is fused to the constant domain of an IgG1 molecule, and (3) gene knockout-failed to negatively affect the therapeutic efficacy of anthracyclines in three distinct tumor models. In particular, TNF α-blocking strategies did not influence the antineoplastic effects of doxorubicin (a prototypic anthracycline) against MCA 205 fibrosarcomas growing in C57BL/6 mice, F244 sarcomas developing in 129/Sv hosts and H2N100 mammary carcinomas arising in BALB/c mice. These findings imply that, in contrast to other cytokines (such as interleukin-1β, interleukin-17 and interferon γ), TNFαis not required for anthracyclines to elicit therapeutic anticancer immune responses.

Original languageEnglish
Article numbere24786
JournalOncoimmunology
Volume2
Issue number6
DOIs
StatePublished - Jun 2013
Externally publishedYes

Keywords

  • Apoptosis
  • Calreticulin
  • Dendritic cell
  • Immunogenic cell death
  • Interferon γ
  • T cells

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