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

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.

A Predictive Biophysical Model of the Combined Action of Radiation Therapy and Immunotherapy of Cancer

“…36,37,45,54 It can therefore enhance lymphocyte action in RIT, potentially increasing the number of responding patients. To spare lymph nodes and keep target volumes small, also modern approaches like stereotactic body radiation therapy, 55 intraoperative radiation therapy, 56 or partial tumor irradiation 19 have demonstrated to preserve or stimulate immune competence. Spatial fractionated dose delivery 57,58 also seems to trigger a sufficient immune response.…”

Long-Term Outcomes of an International Cooperative Study of Intraoperative Radiotherapy Upfront Boost With Low Energy X-Rays in Breast Cancer

“…From an immunological perspective, IORT acts on regulating the surgical cavity environment and pro-inflammatory cytokines, which might be triggered after surgical aggression ( 21 , 22 ). An immediate downregulation of surgically induced tumor-growth factors could potentially yield improved disease-control outcomes, overcoming a temporal miss factor ( 23 – 25 ). Recent data have suggested an improvement in breast cancer mortality for those patients undergoing IORT; nevertheless, different confusing factors might be associated with these differences and further research is warranted to confirm this statement ( 13 , 26 ).…”

Wound Fluid from Breast Cancer Patients Undergoing Intraoperative Radiotherapy Exhibits an Altered Cytokine Profile and Impairs Mesenchymal Stromal Cell Function

“…This observation extends previous findings that the single application of IORT, in contrast to external radiation, does not affect white blood cell counts in peripheral blood samples with a follow-up period up to 4 years [ 19 ]. A recent work also reports unchanged frequencies in Treg, granulocyte and monocyte subsets, yet significantly increased CD56+high CD16+ NK cell numbers 3 weeks after IORT in peripheral blood [ 38 ]. The lower number of monocytes in WF in comparison to the peripheral blood samples may suggest their extravasation into the tissue as part of the local wound healing process [ 39 ].…”