Knoops L et al. (2007) In vivo p53 response and immune reaction underlie highly effective low-dose radiotherapy in follicular lymphoma. Blood 110: 1116–1122

Low-dose involved-field radiotherapy is an effective palliative therapy for patients with follicular lymphoma (FL); however, the molecular mechanisms underlying the response to radiation remain unknown. A study by Knoops et al. used gene-expression analysis to examine the molecular mechanisms involved in radiation sensitivity.

The authors compared the gene-expression profiles of 15 excisional or large-needle biopsy samples removed from patients with FL before and after irradiation. Most of the genes induced by low-dose radiation were identified as being related to at least one of three processes: the p53 pathway; the immune response; or cell-cycle regulation. A Gene Ontology analysis revealed significant over-representations of cell-cycle and immune response genes in the gene set induced by low-dose radiation (P = 0.001 for both). Irradiation also induced the expression of 25 p53-regulated targets. Immunohistochemical analysis confirmed these results, showing an increase in p53-positive cells from 5% before radiation to more than 80% after radiation, as well as demonstrating activation of the intrinsic and extrinsic p53-induced cell death apoptotic pathways. Genes related to the activation of macrophage or dendritic cells, and T-helper-1-related immune responses were also upregulated following irradiation. Immunohistochemical analysis for CD68 and p53 suggested that macrophages might be activated specifically by apoptotic cells to induce apoptotic body clearance.

This is the first in vivo report of an immunologically active, p53 apoptotic response in patients receiving low-dose radiation therapy for FL. Moreover, these results support the use of low-dose radiotherapy as a palliative treatment for patients with FL.