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Stereotactic Ablative Radiotherapy Induces Systemic Differences in Peripheral Blood Immunophenotype Dependent on Irradiated Site
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April 22 2018
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Source: Int J Radiat Oncol Biol Phys. 101(5):1259-1270
Details:
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Alternative Title:Int J Radiat Oncol Biol Phys
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Personal Author:
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Description:Purpose/Objective(s):
Despite strong interest in combining stereotactic ablative radiotherapy (SAR) with immunotherapy, limited data characterize the systemic immune response following SAR. We hypothesized that the systemic immune response to SAR differs by irradiated site due to inherent differences in the microenvironment of various organs.
Materials/Methods:
Patients receiving SAR to any organ underwent prospective blood banking pre- and 1–2 weeks post-SAR. Peripheral blood mononuclear cells (PBMC) and serum were isolated. PBMC were stained with fluorophore-conjugated antibodies against T and natural killer (NK) cell markers. Cells were interrogated by flow cytometry and results were analyzed using Flow Jo software. Serum cytokine and chemokine levels were measured using Luminex. We analyzed changes from pre- to posttherapy with paired t-tests or 1-way ANOVA with Bonferroni’s post-test.
Results:
Thirty-one patients had evaluable PBMC for flow cytometry and thirty-seven had evaluable serum samples for Luminex analysis. Total NK cells and cytotoxic (CD56dim CD16+) NK cells decreased (p = 0.02) and TIM3+ NK cells increased (p = 0.04) following SAR to parenchymal sites (lung and liver), but not to bone or brain. Total memory CD4+ T cells, activated (ICOS+) and CD25+ CD4+ memory T-cells, and activated CD25+ CD8+ memory T cells increased following SAR to parenchymal sites, but not bone or brain. Circulating levels of TNF-α (p = 0.04) and multiple chemokines, including RANTES (p = 0.04), decreased after SAR to parenchymal sites, but not bone or brain.
Conclusions:
Our data suggest SAR to parenchymal sites induces systemic immune changes, including a decrease in total and cytotoxic NK cells, an increase in TIM-3+ NK cells, and an increase in activated memory CD4+ and CD8+ T cells. SAR to non-parenchymal sites did not induce these changes. By comparing the immune response after radiation to different organs, our data suggest SAR induces systemic immunologic changes dependent upon irradiated site.
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Pubmed ID:29891204
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Pubmed Central ID:PMC6364565
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Document Type:
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Funding:P30 CA093373/NCI NIH HHS/National Cancer Institute/United States ; S10 OD018223/ODCDC CDC HHS/Office of the Director/United States ; S10 RR026825/NCRR NIH HHS/National Center for Research Resources/United States ; ZIA BC010944-11/Intramural NIH HHS/Intramural NIH HHS/United States ; K12 CA138464/NCI NIH HHS/National Cancer Institute/United States ; ... More +
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Volume:101
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Issue:5
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