TY - JOUR
T1 - Successful partnerships
T2 - Exploring the potential of immunogenic signals triggered by TMZ, CX-4945, and combined treatment in Gl261 glioblastoma cells
AU - Villamañan, Lucía
AU - Martínez-escardó, Laura
AU - Arús, Carles
AU - Yuste, Victor J.
AU - Candiota, Ana P.
N1 - Publisher Copyright:
© 2021 by the authors. Licensee MDPI, Basel, Switzerland.
PY - 2021/4/1
Y1 - 2021/4/1
N2 - 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.
AB - 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.
KW - ATP
KW - Calreticulin
KW - Cancer immune cycle
KW - Immunogenic signals
KW - Preclinical glioblastoma
KW - Protein kinase CK2
KW - Temozolomide
UR - http://www.scopus.com/inward/record.url?scp=85103053664&partnerID=8YFLogxK
U2 - 10.3390/ijms22073453
DO - 10.3390/ijms22073453
M3 - Article
C2 - 33810611
AN - SCOPUS:85103053664
SN - 1661-6596
VL - 22
JO - International journal of molecular sciences
JF - International journal of molecular sciences
IS - 7
M1 - 3453
ER -