Clonogenicity-based radioresistance determines the expression of immune suppressive immune checkpoint molecules after hypofractionated irradiation of MDA-MB-231 triple-negative breast cancer cells

Gehre S, Meyer F, Sengedorj A, Grottker F, Reichardt C, Alomo J, Borgmann K, Frey B, Fietkau R, Rückert M, Gaipl U (2023)

Publication Type: Journal article

Publication year: 2023

Journal

Frontiers in Oncology Frontiers Media

Book Volume: 13

Article Number: 981239

DOI: 10.3389/fonc.2023.981239

Abstract

Only a subset of patients with triple-negative breast cancer (TNBC) benefits from a combination of radio- (RT) and immunotherapy. Therefore, we aimed to examine the impact of radioresistance and brain metastasizing potential on the immunological phenotype of TNBC cells following hypofractionated RT by analyzing cell death, immune checkpoint molecule (ICM) expression and activation of human monocyte-derived dendritic cells (DCs). MDA-MB-231 triple-negative breast cancer tumor cells were used as model system. Apoptosis was the dominant cell death form of brain metastasizing tumor cells, while Hsp70 release was generally significantly increased following RT and went along with necrosis induction. The ICMs PD-L1, PD-L2, HVEM, ICOS-L, CD137-L and OX40-L were found on the tumor cell surfaces and were significantly upregulated by RT with 5 x 5.2 Gy. Strikingly, the expression of immune suppressive ICMs was significantly higher on radioresistant clones compared to their respective non-radioresistant ones. Although hypofractionated RT led to significant cell death induction and release of Hsp70 in all tumor cell lines, human monocyte-derived DCs were not activated after co-incubation with RT-treated tumor cells. We conclude that radioresistance is a potent driver of immune suppressive ICM expression on the surface of TNBC MDA-MB-231 cells. This mechanism is generally known to predominantly influence the effector phase, rather than the priming phase, of anti-tumor immune responses.

Authors with CRIS profile

Clara Reichardt Department of Medicine 3 – Rheumatology and Immunology Jannik Alomo Medizinische Fakultät Benjamin Frey Department of Radiation Oncology Rainer Fietkau Lehrstuhl für Strahlentherapie Michael Rückert Department of Radiation Oncology Udo Gaipl Department of Radiation Oncology

Involved external institutions

Universitätsklinikum Hamburg-Eppendorf (UKE) DE Germany (DE)

How to cite

APA:

Gehre, S., Meyer, F., Sengedorj, A., Grottker, F., Reichardt, C., Alomo, J.,... Gaipl, U. (2023). Clonogenicity-based radioresistance determines the expression of immune suppressive immune checkpoint molecules after hypofractionated irradiation of MDA-MB-231 triple-negative breast cancer cells. Frontiers in Oncology, 13. https://doi.org/10.3389/fonc.2023.981239

MLA:

Gehre, Simon, et al. "Clonogenicity-based radioresistance determines the expression of immune suppressive immune checkpoint molecules after hypofractionated irradiation of MDA-MB-231 triple-negative breast cancer cells." Frontiers in Oncology 13 (2023).

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