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Anti-Proliferative Effect of Radiotherapy and Implication of Immunotherapy in Anaplastic Thyroid Cancer Cells
Radiotherapy and immunotherapy have shown promising efficacy for the treatment of solid malignancies. Here, we aim to clarify the potential of a combined application of radiotherapy and programmed cell death-ligand 1 (PD-L1) monoclonal antibody atezolizumab in primary anaplastic thyroid cancer (A...
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| Main Authors: | , , , , , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
Philipps-Universität Marburg
2023
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| Subjects: | |
| Online Access: | PDF Full Text |
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| Summary: | Radiotherapy and immunotherapy have shown promising efficacy for the treatment of solid
malignancies. Here, we aim to clarify the potential of a combined application of radiotherapy and
programmed cell death-ligand 1 (PD-L1) monoclonal antibody atezolizumab in primary anaplastic
thyroid cancer (ATC) cells. The radiation caused a significant reduction in cell proliferation, measured
by luminescence, and of the number of colonies. The addition of atezolizumab caused a further reduction
in cell proliferation of the irradiated ATC cells. However, the combined treatment did not cause
either the exposure of the phosphatidylserine or the necrosis, assessed by luminescence/fluorescence.
Additionally, a reduction in both uncleaved and cleaved forms of caspases 8 and 3 proteins was
detectable in radiated cells. The DNA damage evidenced the over-expression of TP53, CDKN1A
and CDKN1B transcripts detected by RT-qPCR and the increase in the protein level of P-
H2AX
and the DNA repair deputed kinases. PD-L1 protein level increased in ATC cells after radiation.
Radiotherapy caused the reduction in cell viability and an increase of PD-L1-expression, but not
apoptotic cell death in ATC cells. The further combination with the immunotherapeutic atezolizumab
could increase the efficacy of radiotherapy in terms of reduction in cell proliferation. Further analysis
of the involvement of alternative cell death mechanisms is necessary to clarify their cell demise
mechanism of action. Their efficacy represents a promising therapy for patients affected by ATC. |
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| Item Description: | Gefördert durch den Open-Access-Publikationsfonds der UB Marburg. |
| DOI: | 10.3390/life13061397 |