Additional file 1: Figure S1. of The in vitro immunogenic potential of caspase-3 proficient breast cancer cells with basal low immunogenicity is increased by hypofractionated irradiation

MCF-7 and MDA-MB231 breast cancer cells in the G2 cell cycle phase after hypofractionated irradiation and/or hyperthermia. MCF-7 (A) or MDA-MB231 (B) tumor cells were treated with hypofractionated irradiation (4x4Gy or 6x3Gy) and/or hyperthermia (41,5 °C for 1 h). Ionizing irradiation was applied 4 h before or after hyperthermia on the first and last day of fractionation. 24 h after the last treatment, the cells were harvested. For determination of the DNA content, the cells were stained with PI in the presence of detergent and analyzed by flow cytometry. The percentage of cells in the G2-phase of the cell cycle is displayed. Representative data of one out of three experiments, each performed in triplicates, are presented as mean ¹ SD. Gy: Gray; HT: hyperthermia; w/o: mock treated control. *p <0,05, **p <0,01 compared to w/o; # p <0,05, ## p <0,01 compared to only irradiated samples. (JPEG 359 kb

Upregulation of heat shock proteins and the promotion of damage-associated molecular pattern signals in a colorectal cancer model by modulated electrohyperthermia

In modulated electrohyperthermia (mEHT) the enrichment of electric field and the concomitant heat can selectively induce cell death in malignant tumors as a result of elevated glycolysis, lactate production (Warburg effect), and reduced electric impedance in cancer compared to normal tissues. Earlier, we showed in HT29 colorectal cancer xenografts that the mEHT-provoked programmed cell death was dominantly caspase independent and driven by apoptosis inducing factor activation. Using this model here, we studied the mEHT-related cell stress 0-, 1-, 4-, 8-, 14-, 24-, 48-, 72-, 120-, 168- and 216-h post-treatment by focusing on damage-associated molecular pattern (DAMP) signals. Significant cell death response upon mEHT treatment was accompanied by the early upregulation (4-h post-treatment) of heat shock protein (Hsp70 and Hsp90) mRNA levels. In situ, the treatment resulted in spatiotemporal occurrence of a DAMP protein signal sequence featured by the significant cytoplasmic to cell membrane translocation of calreticulin at 4 h, Hsp70 between 14 and 24 h and Hsp90 between 24- and 216-h post-treatment. The release of high-mobility group box1 protein (HMGB1) from tumor cell nuclei from 24-h post-treatment and its clearance from tumor cells by 48 h was also detected. Our results suggest that mEHT treatment can induce a DAMP-related signal sequence in colorectal cancer xenografts that may be relevant for promoting immunological cell death response, which need to be further tested in immune-competent animals

Combining RAIT and immune-based therapies to overcome resistance in cancer? Combining RAIT and immune-based therapies to overcome resistance in cancer?

International audienceRadiation therapy has long been considered as immunosuppressive; therefore its impact on the immune system and other aspects which could be involved in raising efficient antitumor immune responses has been neglected. However, the recent demonstration of the immunogenic properties of ionizing radiation is rapidly modifying the radiation oncology field, and it also opens new and promising perspectives for the development and improvement of radioimmunotherapy. In this chapter, we first review the immunogenic properties of irradiation before discussing available evidence of the benefits of radiation therapy and immunotherapy combinations in the context of lymphoma