Nitroaspirin corrects immune dysfunction in tumor-bearing hosts and promotes tumor eradication by cancer vaccination

Carmela De Santo, Paolo Serafini, Ilaria Marigo, Luigi Dolcetti, Manlio Bolla, Piero Del Soldato, Cecilia Melani, Cristiana Guiducci, Mario P. Colombo, Manuela Iezzi, Piero Musiani, Paola Zanovello, Vincenzo Bronte

Research output: Contribution to journalArticle

219 Scopus citations

Abstract

Active suppression of tumor-specific T lymphocytes can limit the immune-mediated destruction of cancer cells. Of the various strategies used by tumors to counteract immune attacks, myeloid suppressors recruited by growing cancers are particularly efficient, often resulting in the induction of systemic T lymphocyte dysfunction. We have previously shown that the mechanism by which myeloid cells from tumor-bearing hosts block immune defense strategies involves two enzymes that metabolize L-arginine: arginase and nitric oxide (NO) synthase. NO-releasing aspirin is a classic aspirin molecule covalently linked to a NO donor group. NO aspirin does not possess direct antitumor activity. However, by interfering with the inhibitory enzymatic activities of myeloid cells, orally administered NO aspirin normalized the immune status of tumor-bearing hosts, increased the number and function of tumor-antigen-specific T lymphocytes, and enhanced the preventive and therapeutic effectiveness of the antitumor immunity elicited by cancer vaccination. Because cancer vaccines and NO aspirin are currently being investigated in independent phase I/II clinical trials, these findings offer a rationale to combine these treatments in subjects with advanced neoplastic diseases.

Original languageEnglish (US)
Pages (from-to)4185-4190
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume102
Issue number11
DOIs
StatePublished - Mar 15 2005

Keywords

  • Arginase
  • Immunosuppression
  • Immunotherapy
  • Myeloid cells
  • Nitric oxide

ASJC Scopus subject areas

  • Genetics
  • General

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  • Cite this

    De Santo, C., Serafini, P., Marigo, I., Dolcetti, L., Bolla, M., Del Soldato, P., Melani, C., Guiducci, C., Colombo, M. P., Iezzi, M., Musiani, P., Zanovello, P., & Bronte, V. (2005). Nitroaspirin corrects immune dysfunction in tumor-bearing hosts and promotes tumor eradication by cancer vaccination. Proceedings of the National Academy of Sciences of the United States of America, 102(11), 4185-4190. https://doi.org/10.1073/pnas.0409783102