Intra-tumoral Salmonella typhimurium induces a systemic anti-tumor immune response that is directed by low-dose radiation to treat distal disease

Francesca Avogadri, Deepak Mittal, Fabiana Saccheri, Massimo Sarrafiore, Mario Ciocca, Paola Larghi, Roberto Orecchia, Maria Rescigno

Research output: Contribution to journalArticle

Abstract

Salmonella typhimurium is a facultative anaerobic bacterium able to multiply preferentially in tumors and inhibit their growth. The mechanisms through which Salmonella exerts its anti-cancer properties are not fully understood. We recently showed that intra-tumoral Salmonella injection results not only in the regression of even bulky tumor masses, but also impacts on the growth of distant untreated lesions. Herewe describe how Salmonella exerts its systemic anti-cancer effects and means to potentiate them. The outburst of an early inflammatory reaction in the treated tumor promotes the development of an immunostimulatory cytokine environment both locally and in the draining lymph node. Within the next 10 days, an efficient cross-presentation of endogenous tumor antigens by dendritic cells at the tumor-draining lymph node leads to the priming of effective anti-tumor CD8+ T cell responses. This potentially broadly reactive T cell repertoire can be directed to other pre-established melanomas by low-dose radiotherapy enhancing the Salmonella anticancer effect. We demonstrate that Salmonella-based therapy coupled to low-dose radiotherapy dampens tumor immune escape mechanisms at different levels and allows controlling systemic disease in a CD8+ T cell-dependent manner.

Original languageEnglish
Pages (from-to)1937-1947
Number of pages11
JournalEuropean Journal of Immunology
Volume38
Issue number7
DOIs
Publication statusPublished - Jul 2008

Keywords

  • Cross-presentation
  • Dendritic cells
  • Radiotherapy
  • Tumor immunity
  • Vaccination

ASJC Scopus subject areas

  • Immunology
  • Immunology and Allergy

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