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Title: Inflammatory and immune reactions in response to chemotherapy-induced cell death
Other Titles: Risposte immuni e infiammatorie indotte dalla chemioterapia
Authors: Sistigu, Antonella
metadata.dc.contributor.advisor: Affabris, Elisabetta
Issue Date: 19-Dec-2011
Publisher: Università degli studi Roma Tre
Abstract: Successful chemotherapy accounts for both tumor-related factors and host immune response. Compelling evidence suggests that some chemotherapeutic agents can and do induce an immunogenic type of cell death stimulating tumor-specific immunity. My PhD Thesis work shows 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 CD8 α+ 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 tumor antigen cross-presentation and T-cell cross-priming, resulting in the induction of a strong antitumor response and tumor rejection. The above mentioned, newly described, effects strongly support the observed powerful capability of CTX and type I IFN to synergize in the induction of antitumor responses in vivo. This study provide new knowledge on type IFN I and CTX, old molecules whose newly described properties can be exploited for the design of innovative clinical protocols in which the generation of effective antitumor immunity is crucially required.
Access Rights: info:eu-repo/semantics/openAccess
Appears in Collections:X_Dipartimento di Biologia
T - Tesi di dottorato

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