Electrochemotherapy with bleomycin induces hallmarks of immunogenic cell death in murine colon cancer cells

Calvet, C.; Famin, Delphine; André, Franck; Mir, Lluis M.

doi:10.4161/onci.28131

Cited by 165 publications

(184 citation statements)

References 61 publications

(83 reference statements)

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“…ICD is characterized by the secretion, release, or surface exposure of damage-associated molecular patterns (DAMPs) [26]. Several preclinical and clinical studies have demonstrated that PDT activates the host immune response [27, 28]; however, the mechanism of how this happens is not clear.…”

Section: Discussionmentioning

confidence: 99%

Immunogenic cell death due to a new photodynamic therapy (PDT) with glycoconjugated chlorin (G-chlorin)

et al. 2016

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Both the pre-apoptotic exposure to calreticulin (CRT) and the post-apoptotic release of high-mobility group box 1 protein (HMGB1) are required for immunogenic cell death. Photodynamic therapy (PDT) uses non-toxic photosensitizers and visible light at a specific wavelength in combination with oxygen to produce cytotoxic reactive oxygen species that kill malignant cells by apoptosis and/or necrosis, shut down the tumor microvasculature, and stimulate the host immune system. We have previously shown that glycoconjugated chlorin (G-chlorin) has superior cancer cell selectivity and effectively suppresses the growth of xenograft tumors. In the present study, we evaluated the immunogenicity of PDT with G-chlorin treatment in colon cancer cells. PDT with G-chlorin suppressed CT26 (mouse colon cancer cells) tumor growth considerably more efficiently in immunocompetent mice (wild-type mice, allograft model) than in immune-deficient mice (nude mice, xenograft model), although control treatments were not different between the two. This treatment also induced CRT translocation and HMGB1 release in cells, as shown by western blot and immunofluorescence staining. To evaluate the use of PDT-treated cells as a tumor vaccine, we employed a syngeneic mouse tumor model (allograft model). Mice inoculated with PDT-treated CT26 cells were significantly protected against a subsequent challenge with live CT26 cells, and this protection was inhibited by siRNA for CRT or HMGB1. In conclusion, PDT with G-chlorin treatment induced immunogenic cell death in a mouse model, where the immunogenicity of this treatment was directed by CRT expression and HMGB1 release.

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Section: Discussionmentioning

confidence: 99%

Immunogenic cell death due to a new photodynamic therapy (PDT) with glycoconjugated chlorin (G-chlorin)

et al. 2016

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“…Moreover, bleomycin has a role in what has been defined the vascular disrupting effect of ECT selectively killing endothelial cells of tumour vessels . Finally, ECT with bleomycin has been recently found to induce evidence of immunogenic cell death in a murine model, suggesting its role in the host immune response against the tumour …”

Section: Introductionmentioning

confidence: 99%

Soft tissue sarcoma in dogs: A treatment review and a novel approach using electrochemotherapy in a case series

Torrigiani

Pierini

Lowe

et al. 2019

Vet Comparative Oncology

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Canine soft tissue sarcomas (STSs) are locally invasive mesenchymal neoplasms. Electrochemotherapy (ECT) is an antitumour local ablative treatment that uses electric pulses to enhance the intracellular delivery of cytotoxic drugs. The aim of this retrospective study was to review the current treatment for STSs and to evaluate the efficacy and safety of ECT with bleomycin in canine STSs. Fifty‐two dogs with 54 STSs were included. Three groups were arranged: (a) ECT alone, (b) intra‐operative ECT and (c) adjuvant ECT. Signalment, tumour size, location, histological grade and margins and ECT parameters were collected. Recurrence rate (RR) and disease‐free interval (DFI) were calculated. Treatment toxicity was assessed using a 6‐point scale. STSs were mostly located on limbs (77.8%). Median tumour size was 4.3 cm (range 0.4‐17.0 cm). Most STSs were grade I (47.7%) and II (50.0%), and histological margins were incomplete in 94.5% of cases. Two complete remissions, one partial remission and one stable disease were recorded in group 1. Group 2 and 3 were similar for tumour location, size and grade, histological margins, treatment toxicity, pulse frequency and voltage. Moreover, RR and DFI were similar between group 2 and 3 (23% and 25%, 81.5 and 243 days, respectively). Local toxicity post ECT was mild (score ≤ 2) in 66.7% of cases. Higher toxicity score was associated with higher pulse voltage (1200 vs 1000 V/cm) (P = 0.0473). ECT coupled with bleomycin resulted safe and efficient in tumour local control and should be considered as an option for treatment of canine STSs.

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“…In this relation, the difference in the response between electrochemotherapy in immunocompetent and in immunodeficient organisms can be attributed to bystander effect, evoked by electroporation or electrochemotherapy (Sersa et al 1997). Furthermore, this can be the starting point for the manipulation of the tumor environment by adjuvant immunotherapy or immune checkpoint inhibitors Calvet et al 2014;Forde et al 2014).…”

Section: Discussionmentioning

confidence: 99%

Bystander Effect Induced by Electroporation is Possibly Mediated by Microvesicles and Dependent on Pulse Amplitude, Repetition Frequency and Cell Type

et al. 2016

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Bystander effect, a known phenomenon in radiation biology, where irradiated cells release signals which cause damage to nearby, unirradiated cells, has not been explored in electroporated cells yet. Therefore, our aim was to determine whether bystander effect is present in electroporated melanoma cells in vitro, by determining viability of non-electroporated cells exposed to medium from electroporated cells and by the release of microvesicles as potential indicators of the bystander effect. Here, we demonstrated that electroporation of cells induces bystander effect: Cells exposed to electric pulses mediated their damage to the non-electroporated cells, thus decreasing cell viability. We have shown that shedding microvesicles may be one of the ways used by the cells to mediate the death signals to the neighboring cells. The murine melanoma B16F1 cell line was found to be more electrosensitive and thus more prone to bystander effect than the canine melanoma CMeC-1 cell line. In B16F1 cell line, bystander effect was present above the level of electropermeabilization of the cells, with the threshold at 800 V/cm. Furthermore, with increasing electric field intensities and the number of pulses, the bystander effect also increased. In conclusion, electroporation can induce bystander effect which may be mediated by microvesicles, and depends on pulse amplitude, repetition frequency and cell type.

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Electrochemotherapy with bleomycin induces hallmarks of immunogenic cell death in murine colon cancer cells

Cited by 165 publications

References 61 publications

Immunogenic cell death due to a new photodynamic therapy (PDT) with glycoconjugated chlorin (G-chlorin)

Immunogenic cell death due to a new photodynamic therapy (PDT) with glycoconjugated chlorin (G-chlorin)

Soft tissue sarcoma in dogs: A treatment review and a novel approach using electrochemotherapy in a case series

Bystander Effect Induced by Electroporation is Possibly Mediated by Microvesicles and Dependent on Pulse Amplitude, Repetition Frequency and Cell Type

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