M1 microglia polarization induced by radiotherapy and dendritic cell immunotherapy combination.
PO-1827
Abstract
M1 microglia polarization induced by radiotherapy and dendritic cell immunotherapy combination.
Authors: Valentina Pinzi1,2, Natalia Di Ianni3, Maria Luisa Fumagalli4, Martina Maffezzini3, Laura Fariselli5, Serena Pellegatta3
1Fondazione IRCCS Istituto neurologico Carlo Besta, Neurosurgery, Radiotherapy Unit, Milan, Italy; 2University of Milan-Bicocca, Neuroscience, Milan, Italy; 3Fondazione IRCCS Istituto neurologico Carlo Besta, Unit of Immunotherapy of Brain Tumors, Unit of Molecular Neuro-Oncology, Milan, Italy; 4Fondazione IRCCS Istituto neurologico Carlo Besta, Health Department, Milan, Italy; 5Fondazione IRCCS Istituto neurologico Carlo Besta, Radiotherapy Unit, Neurosurgery Department, Milan, Italy
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Purpose or Objective
Radiotherapy (RT),
providing immunomodulation on tumor microenvironment, can increase the
sensitivity to the specific immune response of cold tumors such as glioblastoma
(GBM). To investigate the RT effects as both exclusive and combinatorial
strategies with immunotherapy (IT), we treated immune-competent glioma-bearing
mice with both local fractionated RT and RT followed by dendritic cell (DC) IT.
Material and Methods
GL261-glioma bearing mice were locally irradiated with
a total dose of 15 Gy in 3 consecutive fractions of 5 Gy on day 7, 8, and 9
after tumor implantation. For combinatorial treatment, DC-IT were injected
subcutaneously on day 16, 23, and 30 after tumor implantation. Changes in tumor
microenvironment were investigated by assessing microglial and chemokine gene
expression on gliomas of RT, RT-IT treated and control mice. The microglia cells from explanted tumours were analyzed as well.
Results
RT promoted a
polarization from M2 to M1 of microglia/macrophages (GAMs) within the
microenvironment, characterized by increased production of pro-inflammatory
antitumor cytokines such as TNF-α and IFN-γ and high level of iNOS. Indeed, M2
phenotype markers, TGF-β1 and IL-10, were significantly decreased in irradiated
mice at the earlier time point (day 16). Moreover, RT-IT influenced
CD45dim/CD11b+/CD172A+ microglia activation, characterized by a M1 signature, and
CD4+ T cells recruitment as well as a robust infiltration of CD8+ T cells. The
overall survival of glioma-bearing mice was higher in the RT-IT group.
Conclusion
Our preliminary data suggest that the RT-IT
combination is efficient in promoting a proinflammatory microenvironment and
re-educating microglia as anti-tumor effector cells.