Successful partnerships: Exploring the potential of immunogenic signals triggered by TMZ, CX-4945, and combined treatment in Gl261 glioblastoma cells

Lucía Villamañan, Laura Martínez-escardó, Carles Arús, Victor J. Yuste, Ana P. Candiota*

*Autor corresponent d’aquest treball

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Resum

Background: The relevance of the cancer immune cycle in therapy response implies that successful treatment may trigger the exposure or the release of immunogenic signals. Previous results with the preclinical GL261 glioblastoma (GB) showed that combination treatment of te-mozolomide (TMZ) + CX-4945 (protein kinase CK2 inhibitor) outperformed single treatments, pro-vided an immune-friendly schedule was followed. Our purpose was to study possible immuno-genic signals released in vitro by GB cells. Methods: GL261 GB cells were treated with TMZ and CX-4945 at different concentrations (25 μM–4 mM) and time frames (12–72 h). Cell viability was measured with Trypan Blue and propidium iodide. Calreticulin exposure was assessed with immu-nofluorescence, and ATP release was measured with bioluminescence. Results: TMZ showed cyto-static rather than cytotoxic effects, while CX-4945 showed remarkable cytotoxic effects already at low concentrations. Calreticulin exposure after 24h was detected with TMZ treatment, as well as TMZ/CX-4945 low concentration combined treatment. ATP release was significantly higher with CX-4945, especially at high concentrations, as well as with TMZ/CX-4945. Conclusions: combined treatment may produce the simultaneous release of two potent immunogenic signals, which can explain the outperformance over single treatments in vivo. A word of caution may be raised since in vitro conditions are not able to mimic pharmacokinetics observed in vivo fully.

Idioma originalAnglès
Número d’article3453
Nombre de pàgines18
RevistaInternational journal of molecular sciences
Volum22
Número7
DOIs
Estat de la publicacióPublicada - 1 d’abr. 2021

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