Abstract

A detailed understanding of the interactions and the best dose-fractionation scheme of radiation to maximize antitumor immunity have not been fully established. In this study, the effect on the host immune system of a single dose of 20 Gy through intraoperative radiation therapy (IORT) on the surgical bed in low-risk breast cancer patients undergoing conserving breast cancer has been assessed. Peripheral blood samples from 13 patients were collected preoperatively and at 48 h and 3 and 10 weeks after the administration of radiation. We performed a flow cytometry analysis for lymphocyte subpopulations, natural killer cells (NK), regulatory T cells (Treg) and myeloid-derived suppressor cells (MDSCs). We observed that the subpopulation of NK CD56+high CD16+ increased significantly at 3 weeks after IORT (0.30–0.42%, P < 0.001), while no changes were found in immunosuppressive profile, CD4+CD25+Foxp3+Helios+ Treg cells, granulocytic MDSCs (G-MDSCs) and monocytic MDSCs (Mo-MDSCs). A single dose of IORT may be an effective approach to improve antitumor immunity based on the increase in NK cells and the non-stimulation of immunosuppressive cells involved in immune escape. These findings support future combinations of IORT with immunotherapy, if they are confirmed in a large cohort of breast cancer patients.

Highlights

  • Breast cancer is the most common malignancy and the second highest cause of death in women worldwide [1]

  • Results presented in this study indicate that treatment with intraoperative radiation therapy (IORT) in low-risk breast cancer patients undergoing conserving breast surgery can affect the balance of immune cells in the peripheral blood

  • We noted that radiation therapy increased the presence of peripheral natural killer cells (NK) cells while no changes were detected in the immunosuppressive profile, characterized by Treg cells and myeloid-derived suppressor cells (MDSCs)

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Summary

Introduction

Breast cancer is the most common malignancy and the second highest cause of death in women worldwide [1]. The current treatment for early-stage breast cancer is breast conservation surgery followed by radiation therapy. Changes in peripheral immune cells after intraoperative radiation therapy in low-risk breast cancer 111. The results indicate that treatment with intraoperative radiation therapy (IORT) yields similar results in terms of survival and toxicity as whole-breast radiation therapy, with the benefit of reduced treatment time. In this context, IORT has been established as a good option for patients’ treatment in early-stage breast cancer undergoing conserving surgery, or in combination with external beam radiation therapy (EBRT) in patients with risk factors [4, 6]

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