Sarcoma eradication by doxorubicin and targeted TNF relies upon CD8+ T-cell recognition of a retroviral antigen

Philipp Probst, Janine Kopp, Annette Oxenius, Mario P. Colombo, Danilo Ritz, Tim Fugmann, Dario Neri

Research output: Contribution to journalArticle

Abstract

Antibody–cytokine complexes may offer new tools to treat cancer. Here, we show how TNF-linked antibodies, which recognize tumor-selective splice isoforms of fibronectin (F8-TNF), can be exploited to eradicate sarcomas in immunocompetent mice. We treated mice bearing WEHI-164 fibrosarcoma with a combination of F8-TNF and doxorubicin, curing the majority of treated animals (29/37). Notably, cured mice were resistant to rechallenge not only by WEHI-164 cells but also heterologous C51 or CT26 colorectal tumor cells in a CD8+ T-cell–dependent process. Mechanistic analyses revealed that each tumor cell line presented AH1, a common endogenous retroviral peptide. Numbers of AH1-specific CD8+ T cells exhibiting cytotoxic capacity were increased by F8-TNF plus doxorubicin treatment, arguing that cognate CD8+ T cells contributed to tumor eradication. Sequence analysis of T-cell receptors of CD8+ T cells revealed the presence of H-2Ld/AH1-specific T cells and an expansion of sequence diversity in treated mice. Overall, our findings provide evidence that retroviral genes contribute to tumoral immunosurveillance in a process that can be generally boosted by F8-TNF and doxorubicin treatment.

Original languageEnglish
Pages (from-to)3644-3654
Number of pages11
JournalCancer Research
Volume77
Issue number13
DOIs
Publication statusPublished - Jul 1 2017

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ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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