Combination of Ionising Irradiation and Hyperthermia Activates Programmed Apoptotic and Necrotic Cell Death Pathways in Human Colorectal Carcinoma Cells

Mantel, Frederick; Frey, Benjamin; Haslinger, Stefan; Schildkopf, Petra; Sieber, Renate; Ott, Oliver J.; Lödermann, Barbara; Rödel, Franz; Sauer, Rolf; Fietkau, Rainer; Gaipl, Udo S.

doi:10.1007/s00066-010-2154-x

Cited by 51 publications

(31 citation statements)

References 38 publications

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“…Though our results cannot be linked directly to ICD, detection of DAMP signals in colon cancer supports the feasibility of testing if mEHT treatment can directly promote ICD in tumors raised in immune competent animals. In conclusion, based on sporadic observations of earlier in vitro studies of local hyperthermia (Frey et al 2012;Mantel et al 2010;Schildkopf et al 2010), here, we showed, in vivo, that mEHT induced tumor cell stress can generate the spatiotemporal sequence of DAMP signals in colorectal cancer without any additional genetic or pharmaceutical intervention. Our data suggest that mEHT can be a potential local inducer of ICD, without a systemic interference with immune functions, which need to be investigated further in immune competent animal models.…”

Section: Discussionmentioning

confidence: 96%

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

Andócs

Meggyesházi

Balogh

et al. 2015

Cell Stress and Chaperones

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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 mEHTprovoked 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.

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Section: Discussionmentioning

confidence: 96%

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

Andócs

Meggyesházi

Balogh

et al. 2015

Cell Stress and Chaperones

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“…118 Also HMGB1 release was detected after HT treatment of tumor cells lines at high temperature of 56 C. 59 The current paradigm of the immunogenicity of HT lies in the action of HSP70 and/or other released heat shock proteins which via TLR4 signaling play the main role in the initiation of tumorspecific immune responses. 111,112,119,120 It has been shown that the combination of HT and RT (X-rays or UVC) induces an inflammatory necrotic tumor death which can be monitored by the release of HMGB1 and HSP70 121,122 and stimulation of DC maturation and release of pro-inflammatory cytokines. 59,123 Currently there are no clinical data on the use of HT-killed tumor cells alone in clinical protocols.…”

Section: Photodynamic Therapymentioning

confidence: 99%

Physical modalities inducing immunogenic tumor cell death for cancer immunotherapy

et al. 2014

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“…Clonogenic assays were conducted with a single-cell suspension of exponentially-growing SW480 colorectal tumor cells as previously described (Mantel et al, 2010). Briefly, counted cells were plated into petri dishes (Nunc Thermo Fisher, Waltham, MA) with growth-medium and irradiated 24 h after plating.…”

Section: Analysis Of the Clonogenic Potentialmentioning

confidence: 99%

Norm- and hypo-fractionated radiotherapy is capable of activating human dendritic cells

Kulzer¹,

Rubner²,

Deloch³

et al. 2014

Journal of Immunotoxicology

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Despite the transient immunosuppressive properties of local radiotherapy (RT), this classical treatment modality of solid tumors is capable of inducing immunostimulatory forms of tumor-cell death. The resulting 'immunotoxicity' in the tumor, but not in healthy tissues, may finally lead to immune-mediated destruction of the tumor. However, little is known about the best irradiation scheme in this setting. This study examines the immunological effects of differently irradiated human colorectal tumor cells on human monocyte-derived dendritic cells (DC). Human SW480 tumor cells were irradiated with a norm-fractionation scheme (5 Â 2 Gy), a hypo-fractionated protocol (3 Â 5 Gy), and with a high single irradiation dose (radiosurgery; 1 Â 15 Gy). Subsequently, human immature DC (iDC) were co-incubated with supernatants (SN) of these differently treated tumor cells. Afterwards, DC were analyzed regarding the expression of maturation markers, the release of cytokines, and the potential to stimulate CD4 + T-cells. The co-incubation of iDC with SN of tumor cells exposed to norm-or hypo-fractionated RT resulted in a significantly increased secretion of the immune activating cytokines IL-12p70, IL-8, IL-6, and TNF, compared to iDC co-incubated with SN of tumor cells that received a high single irradiation dose or were not irradiated. In addition, DC-maturation markers CD80, CD83, and CD25 were also exclusively elevated after co-incubation with the SN of fractionated irradiated tumor cells. Furthermore, the SN of tumor cells that were irradiated with norm-or hypo-fractionated RT triggered iDC to stimulate CD4 + T-cells not only in an allogenic, but also in an antigen-specific manner like mature DC. Collectively, these results demonstrate that norm-and hypo-fractionated RT induces a fast human colorectal tumor-cell death with immunogenic potential that can trigger DC maturation and activation in vitro. Such findings may contribute to the improvement of irradiation protocols for the most beneficial induction of anti-tumor immunity.

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Combination of Ionising Irradiation and Hyperthermia Activates Programmed Apoptotic and Necrotic Cell Death Pathways in Human Colorectal Carcinoma Cells

Abstract: The combined treatment of colorectal tumor cells with X-ray and HT activates distinct tumor cell pathways and fosters the early appearance of a necrotic tumor cell phenotype.

Cited by 51 publications

References 38 publications

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

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

Physical modalities inducing immunogenic tumor cell death for cancer immunotherapy

Norm- and hypo-fractionated radiotherapy is capable of activating human dendritic cells

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