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

作者：Ma Yuting; Yamazaki Takahiro; Yang Heng; Kepp Oliver; Galluzzi Lorenzo; Zitvogel Laurence^*; Smyth Mark J; Kroemer Guido

来源：OncoImmunology, 2013, 2(6): UNSP e24786.

DOI：10.4161/onci.24786

• apoptosis
• calreticulin
• dendritic cell
• immunogenic cell death
• interferon gamma
• T cells

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 (TNF). However, blocking the TNF/TNF receptor (TNFR) system by three different strategiesnamely, (1) neutralizing antibodies, (2) etanercept, a recombinant protein in which TNFR is fused to the constant domain of an IgG(1) molecule, and (3) gene knockoutfailed to negatively affect the therapeutic efficacy of anthracyclines in three distinct tumor models. In particular, TNF-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-1, interleukin-17 and interferon ), TNF is not required for anthracyclines to elicit therapeutic anticancer immune responses.

• 出版日期2013-6-1
• 单位河北医科大学