Personalized Nutrition as a Key Contributor to Improving Radiation Response in Breast Cancer

Understanding metabolic and immune regulation inherent to patient populations is key to improving the radiation response for our patients. To date, radiation therapy regimens are prescribed based on tumor type and stage. Patient populations who are noted to have a poor response to radiation such as those of African American descent, those who have obesity or metabolic syndrome, or senior adult oncology patients, should be considered for concurrent therapies with radiation that will improve response. Here, we explore these populations of breast cancer patients, who frequently display radiation resistance and increased mortality rates, and identify the molecular underpinnings that are, in part, responsible for the radiation response and that result in an immune-suppressive tumor microenvironment. The resulting immune phenotype is discussed to understand how antitumor immunity could be improved. Correcting nutrient deficiencies observed in these populations should be considered as a means to improve the therapeutic index of radiation therapy.

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

Journal of Radiation Research ◽

10.1093/jrr/rraa083 ◽

2020 ◽

Vol 62 (1) ◽

pp. 110-118

Author(s):

Isabel Linares-Galiana ◽

Miguel Angel Berenguer-Frances ◽

Rut Cañas-Cortés ◽

Monica Pujol-Canadell ◽

Silvia Comas-Antón ◽

...

Keyword(s):

Breast Cancer ◽

Radiation Therapy ◽

Single Dose ◽

Cancer Patients ◽

Antitumor Immunity ◽

Low Risk ◽

Intraoperative Radiation Therapy ◽

Breast Cancer Patients ◽

Intraoperative Radiation ◽

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.

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Tribbles Homolog 3 Involved in Radiation Response of Triple Negative Breast Cancer Cells by Regulating Notch1 Activation

Cancers ◽

10.3390/cancers11020127 ◽

2019 ◽

Vol 11 (2) ◽

pp. 127 ◽

Cited By ~ 10

Author(s):

Yueh-Chun Lee ◽

Wen-Ling Wang ◽

Wei-Chao Chang ◽

Yu-Hao Huang ◽

Guan-Ci Hong ◽

...

Keyword(s):

Breast Cancer ◽

Radiation Therapy ◽

Cancer Patients ◽

Triple Negative ◽

Mass Spectrometry Analysis ◽

Radiation Response ◽

Stem Cell Population ◽

Breast Cancers ◽

Breast Cancer Patients ◽

Poor Prognostic Factor

Breast cancer is the most common cancer for women in Taiwan and post-lumpectomy radiotherapy is one of the therapeutic strategies for this malignancy. Although the 10-year overall survival of breast cancer patients is greatly improved by radiotherapy, the locoregional recurrence is around 10% and triple negative breast cancers (TNBCs) are at a high risk for relapse. The aim of this paper is to understand the mechanisms of radioresistance in breast cancers which may facilitate the development of new treatments in sensitizing breast cancer toward radiation therapy. Tribbles homolog 3 (TRIB3) is a pseudokinase protein and known to function as a protein scaffold within cells. It has been reported that higher TRIB3 expression is a poor prognostic factor in breast cancer patients with radiotherapy. In this study, we investigate the involvement of TRIB3 in the radiation response of TNBC cells. We first found that the expression of TRIB3 and the activation of Notch1, as well as Notch1 target genes, increased in two radioresistant TNBC cells. Knockdown of TRIB3 in radioresistant MDA-MB-231 TNBC cells decreased Notch1 activation, as well as the CD24-CD44+ cancer stem cell population, and sensitized cells toward radiation treatment. The inhibitory effects of TRIB3 knockdown in self-renewal or radioresistance could be reversed by forced expression of the Notch intracellular domain. We also observed an inhibition in cell growth and accumulated cells in the G0/G1 phase in radioresistant MDA-MB-231 cells after knockdown of TRIB3. With immunoprecipitation and mass spectrometry analysis, we found that, BCL2-associated transcription factor 1 (BCLAF1), BCL2 interacting protein 1 (BNIP1), or DEAD-box helicase 5 (DDX5) were the possible TRIB3 interacting proteins and immunoprecipitation data also confirmed that these proteins interacted with TRIB3 in radioresistant MDA-MB-231 cells. In conclusion, the expression of TRIB3 in radioresistant TNBC cells participated in Notch1 activation and targeted TRIB3 expression may be a strategy to sensitize TNBC cells toward radiation therapy.

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