title: Tumor necrosis factor is dispensable for the success of immunogenic anticancer chemotherapy.
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 α (TNFα). However, blocking the TNFα/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 IgG1molecule, and (3) gene knockout-failed to negatively affect the therapeutic efficacy of anthracyclines in three distinct tumor models. In particular, TNFα-blocking strategies did not influence the antineoplastic effects of doxorubicin (a prototypic anthracycline) against MCA205 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), TNFα is not required for anthracyclines to elicit therapeutic anticancer immune responses.
authors.affiliation: INSERM, U848; Villejuif, France ; Institut Gustave Roussy, Villejuif, France ; Université Paris Sud/Paris XI; Le Kremlin Bicêtre; Paris, France.
authors.forename: Yuting
authors.initials: Y
authors.lastname: Ma
authors.forename: Takahiro
authors.initials: T
authors.lastname: Yamazaki
authors.forename: Heng
authors.initials: H
authors.lastname: Yang
authors.forename: Oliver
authors.initials: O
authors.lastname: Kepp
authors.forename: Lorenzo
authors.initials: L
authors.lastname: Galluzzi
authors.forename: Laurence
authors.initials: L
authors.lastname: Zitvogel
authors.forename: Mark J
authors.initials: MJ
authors.lastname: Smyth
authors.forename: Guido
authors.initials: G
authors.lastname: Kroemer
keywords: T cells; apoptosis; calreticulin; dendritic cell; immunogenic cell death; interferon γ
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