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 IgG1 molecule, 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: Yuting Ma, Takahiro Yamazaki, Heng Yang, Oliver Kepp, Lorenzo Galluzzi, Laurence Zitvogel, Mark J Smyth, Guido Kroemer
• Journal: Oncoimmunology (Oncoimmunology) Vol. 2 Issue 6 Pg. e24786 (Jun 01 2013) ISSN: 2162-4011 [Print] United States
• PMID: 23894723 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)