Preliminary Study of the Effect of Stereotactic Body Radiotherapy (SBRT) on the Immune System in Lung Cancer Patients Unfit for Surgery: Immunophenotyping Analysis

Abstract

An immunophenotyping analysis was performed in peripheral blood samples from seven patients with lung cancer unfit for surgery treated with stereotactic body radiotherapy (SBRT). The objective was to characterize the effect of SBRT on the host immune system. Four patients received 60 Gy (7.5 Gy × 8) and three 50 Gy (12.5 Gy × 4). Analyses were performed before SBRT, 72 h after SBRT, and at one, three, and six months after the end of SBRT. Of note, there was a specific increase of the immunoactive component of the immune system, with elevation of CD56+highCD16+ natural killer (NK) cells (0.95% at baseline to 1.38% at six months), and a decrease of the immunosuppressive component of the immune system, with decreases of CD4+CD25+Foxp3+CDA5RA− regulatory T cells (4.97% at baseline to 4.46% at six months), granulocytic myeloid-derived suppressor cells (G-MDSCs) (from 66.1% at baseline to 62.6% at six months) and monocytic (Mo-MDSCs) (8.2% at baseline to 6.2% at six months). These changes were already apparent at 72 h and persisted over six months. SBRT showed an effect on systemic immune cell populations, which is a relevant finding for supporting future combinations of SBRT with immunotherapy for treating lung cancer patients.

Myeloid-derived suppressor cells—new and exciting players in lung cancer

“…The study provided novel evidence that SBRT had a systemic effect on the immune system. The observation that both CD33 + CD11b + CD14 − PMN-MDSCs and CD33 + CD11b + CD14 + HLA-DR −/low M-MDSCs exhibited decreases in immunosuppressive function is a salient finding of the study [27].…”

“…However, there are still no uniform standards for surface molecular markers of human MDSCs, and many other markers are being reported gradually. From the perspective of LC, according to multicolor immunofluorescence staining evaluated by fluorescenceactivated cell sorting (FACS), the following phenotypes of MDSCs have been reported (shown in Table 1): CD11b + CD14 − CD15 + CD33 + [14], CD11b + CD14 + S100A9 + [15], CD16 low CD11b + CD14 − HLA-DR − CD15 + CD33 + [16], CD14 + HLA-DR −/low [17,18], B7-H3 + CD14 + HLA-DR −/low [19], CD11b + CD14 − HLA-DR − CD33 + CD15 + ILT3 high [20], Lin − CD14 − CD11b + CD39 + CD73 + [21], Lin − CD14 + CD11b + C D39 + CD73 + [21], Lin − CD14 + CD15 + H LA-DR − [22], Lin − C D14 + CD15 − HLA-DR − [22], Lin − CD14 − HLA-DR − [22], Lin-CD33 + CD14 + CD15 − HLA-DR − [25], CD33 + CD11b + CD14 − [27], CD33 + CD11b + CD14 + HLA-DR −/low [27], and CCR 5 + HLA-DR −/low CD11b + CD14 + CD15 − [28].…”

Changes in peripheral immune cells after intraoperative radiation therapy in low-risk breast cancer

“…Indeed a significant decrease in the percentage of granulocytes was observed 6 months after the administration of radiation. These results may show the possible benefit of the application of this type of scheme, which seems to be more effective in controlling cells related to immunosuppression [ 40 ].…”

Immunomodulation of NK Cells by Ionizing Radiation

“…Other publications have shed light on the impact of SBRT on lung cancer. A detectable augmentation of CD56 high CD16 + NK cell frequency persisting throughout 6 months without statistically importance compared to baseline was observed in blood samples of lung cancer patients administrated with SBRT (7.5 Gy × 8 or 12.5 Gy × 4) (134). Quite the reverse occured, as another clinical research enrolling a larger cohort of lung cancer patients received a total dose ranging from 40 to 70 Gy fractionated into 4-10 days (single doses ranging from 6 Gy to 15 Gy, with most patients received single doses ranging from 10 Gy to 15 Gy) revealed decreased NK counts and activity immediately and at 1 week post-IR without the alteration of NK ratio in periphery (135).…”