In vivo p53 response and immune reaction underlie highly effective low-dose radiotherapy in follicular lymphoma
2007; Elsevier BV; Volume: 110; Issue: 4 Linguagem: Inglês
10.1182/blood-2007-01-067579
ISSN1528-0020
AutoresLaurent Knoops, Rick L. Haas, Sanne R. Martens‐de Kemp, Donné Majoor, Annegien Broeks, Eric Eldering, Jan Paul de Boer, Marcel Verheij, Conny van Ostrom, Annemieke de Vries, Laura van’t Veer, Daphne de Jong,
Tópico(s)Viral-associated cancers and disorders
ResumoVery low-dose irradiation (2 x 2 Gy) is a new, effective, and safe local treatment for follicular lymphoma. To understand the biologic mechanisms of this extremely effective response, we compared by microarray the gene-expression profile of patients' biopsies taken before and after radiation. In all patients, a major and consistent induction of p53 target genes was seen. p53 targets involved in cell-cycle arrest and apoptosis showed the same mode of regulation, indicating that, in vivo, both are activated simultaneously. p53 up-regulation and p53-mediated proliferation arrest and apoptosis were substantiated using immunohistochemistry, with activation of both the intrinsic and the extrinsic apoptotic pathways. The other induced genes revealed a whole set of biologically meaningful genes related to macrophage activation and TH1 immune response. Immunohistochemical analysis suggested a specific activation or differentiation of resident macrophages by apoptotic cells. These biologic insights are important arguments to advocate the use of low-dose radiotherapy as an effective palliative treatment for follicular lymphoma. Moreover, this study is the first in vivo report of the radiation-induced p53 apoptotic response in patients and suggests that this apoptotic response is not immunologically silent.
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