00085472can162946-sup-173847_3_supp_3989644_kknpvd.docx (1.44 MB)
Figure S1 from Sarcoma Eradication by Doxorubicin and Targeted TNF Relies upon CD8+ T-cell Recognition of a Retroviral Antigen
journal contribution
posted on 2023-03-31, 00:48 authored by Philipp Probst, Janine Kopp, Annette Oxenius, Mario P. Colombo, Danilo Ritz, Tim Fugmann, Dario NeriImmunofluorescence analysis with MHC I tetramers on spleen and tumor sections
Funding
Swiss National Science Foundation
National Natural Science Foundation of China
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ARTICLE 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. Cancer Res; 77(13); 3644–54. ©2017 AACR.Usage metrics
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