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 language | English |
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Article number | e24786 |
Journal | Oncoimmunology |
Volume | 2 |
Issue number | 6 |
DOIs | |
State | Published - Jun 2013 |
Externally published | Yes |
Keywords
- Apoptosis
- Calreticulin
- Dendritic cell
- Immunogenic cell death
- Interferon γ
- T cells