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 IFN-I, 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.
journal_name
Cancer Resjournal_title
Cancer researchauthors
Schiavoni G,Sistigu A,Valentini M,Mattei F,Sestili P,Spadaro F,Sanchez M,Lorenzi S,D'Urso MT,Belardelli F,Gabriele L,Proietti E,Bracci Ldoi
10.1158/0008-5472.CAN-10-2788subject
Has Abstractpub_date
2011-02-01 00:00:00pages
768-78issue
3eissn
0008-5472issn
1538-7445pii
0008-5472.CAN-10-2788journal_volume
71pub_type
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