Detailed in vitro analyses of the impact of multimodal cancer therapy with hyperthermia and radiotherapy on the immune phenotype of human glioblastoma cells

Stoll E, Hader M, Rückert M, Weissmann T, Lettmaier S, Putz F, Hecht M, Fietkau R, Rosin A, Frey B, Gaipl U (2022)

Publication Type: Journal article

Publication year: 2022

Journal

International Journal of Hyperthermia Informa Healthcare

Book Volume: 39

Pages Range: 796-805

Journal Issue: 1

DOI: 10.1080/02656736.2022.2080873

Abstract

Purpose Improvements of heat-delivery systems have led to hyperthermia (HT) being increasingly recognized as an adjunct treatment modality also for brain tumors. But how HT affects the immune phenotype of glioblastoma cells is only scarcely known. Materials and Methods We therefore investigated the effect of in vitro HT, radiotherapy (RT), and the combination of both (RHT) on cell death modalities, immune checkpoint molecule (ICM) expression and release of the danger signal HSP70 of two human glioblastoma cell lines (U87 and U251) by using multicolor flow cytometry and ELISA. Hyperthermia was performed once or twice for 60-minute sessions reaching temperatures of 39 degrees C, 41 degrees C, and 44 degrees C, respectively. RT was administered with 5 x 2 Gy. Results A hyperthermia chamber for cell culture t-flasks regulating the temperature via a contact sensor was developed. While the glioblastoma cells were rather radioresistant, particularly in U251 cells, the combination of RT with HT significantly increased the percentage of apoptotic and necrotic cells for all temperatures examined and for both, single and double HT application. In line with that, an increased release of HSP 70 was seen only in U251 cells, mainly following treatment with HT at temperatures of 44 degrees C alone or in combination with RT. In contrast, immune suppressive (PD-L1, PD-L2, HVEM) and immune stimulatory (ICOS-L, CD137-L and Ox40-L) ICMs were significantly increased mostly on U87 cells, and particularly after RHT with 41 degrees C. Conclusions Individual assessment of the glioblastoma immune cell phenotype with regard to the planned treatment is mandatory to optimize multimodal radio-immunotherapy protocols including HT.

Authors with CRIS profile

Michael Hader Department of Radiation Oncology Michael Rückert Department of Radiation Oncology Thomas Weissmann Department of Radiation Oncology Florian Putz Department of Radiation Oncology Markus Hecht Department of Radiation Oncology Rainer Fietkau Lehrstuhl für Strahlentherapie Benjamin Frey Department of Radiation Oncology Udo Gaipl Department of Radiation Oncology

Involved external institutions

Universität Bayreuth DE Germany (DE)

How to cite

APA:

Stoll, E., Hader, M., Rückert, M., Weissmann, T., Lettmaier, S., Putz, F.,... Gaipl, U. (2022). Detailed in vitro analyses of the impact of multimodal cancer therapy with hyperthermia and radiotherapy on the immune phenotype of human glioblastoma cells. International Journal of Hyperthermia, 39(1), 796-805. https://doi.org/10.1080/02656736.2022.2080873

MLA:

Stoll, Eileen, et al. "Detailed in vitro analyses of the impact of multimodal cancer therapy with hyperthermia and radiotherapy on the immune phenotype of human glioblastoma cells." International Journal of Hyperthermia 39.1 (2022): 796-805.

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