Cyclophosphamide synergizes with type I interferons through systemic dendritic cell reactivation and induction of immunogenic tumor apoptosis

Giovanna Schiavoni, Antonella Sistigu, Mara Valentini, Fabrizio Mattei, Paola Sestili, Francesca Spadaro, Massimo Sanchez, Silvia Lorenzi, Maria Teresa D'Urso, Filippo Belardelli, Lucia Gabriele, Enrico Proietti, Laura Bracci

Research output: Contribution to journalArticlepeer-review

Abstract

Successful chemotherapy accounts for both tumor-related factors and host immune response. Compelling evidence suggests that some chemotherapeutic agents can induce an immunogenic type of cell death stimulating tumor-specific immunity. Here, we show that cyclophosphamide (CTX) exerts two types of actions relevant for the induction of antitumor immunity in vivo: (i) effect on dendritic cell (DC) homeostasis, mediated by endogenous type I interferons (IFN-I), leading to the preferential expansion of CD8α+ DC, the main subset involved in the cross-presentation of cell-derived antigens; and (ii) induction of tumor cell death with clear-cut immunogenic features capable of stimulating tumor infiltration, engulfment of tumor apoptotic material, and CD8 T-cell cross-priming by CD8α+ DC. Notably, the antitumor effects of CTX were efficiently amplified by IFNI, the former providing a source of antigen and a "resetting" of the DC compartment and the latter supplying optimal costimulation for T-cell cross-priming, resulting in the induction of a strong antitumor response and tumor rejection. These results disclose new perspectives for the development of targeted and more effective chemoimmunotherapy treatments of cancer patients.

Original languageEnglish
Pages (from-to)768-778
Number of pages11
JournalCancer Research
Volume71
Issue number3
DOIs
Publication statusPublished - Feb 1 2011

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

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