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Poster display session: Biomarkers, Gynaecological cancers, Haematological malignancies, Immunotherapy of cancer, New diagnostic tools, NSCLC - early stage, locally advanced & metastatic, SCLC, Thoracic malignancies, Translational research

2613 - Adjuvant radiation therapy leads to an up-regulation of programmed death ligand 1 (PD-L1) on circulating epithelial tumor cells (CETCs) which might contribute to radioresistance in primary breast cancer patients

Date

20 Oct 2018

Session

Poster display session: Biomarkers, Gynaecological cancers, Haematological malignancies, Immunotherapy of cancer, New diagnostic tools, NSCLC - early stage, locally advanced & metastatic, SCLC, Thoracic malignancies, Translational research

Topics

Tumour Immunology;  Radiation Oncology

Tumour Site

Breast Cancer

Presenters

Dorothea Schott

Citation

Annals of Oncology (2018) 29 (suppl_8): viii14-viii57. 10.1093/annonc/mdy269

Authors

D. Schott1, M. Pizon1, U. Pachmann1, K. Pachmann1, M. Mäurer2

Author affiliations

  • 1 Transfusion Center Bayreuth, Transfusion Center Bayreuth, 95448 - Bayreuth/DE
  • 2 Radiooncology, University Hospital of Jena, 07743 - Jena/DE
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Resources

Abstract 2613

Background

Radiation therapy (RT) is an integral part of the treatment of breast carcinoma but unfortunately many patients experience local recurrence. During the inflammatory response that accompanies radiation tumor cells may develop multiple resistance mechanisms for example the up-regulation of PD-L1 on tumor cells which leads to immune evasion. Since CETCs arise from the tumor it is conceivable that under evolutionary pressure they might share some of the immune escape mechanism inherent to tumor cells. In this study we demonstrate that RT leads to a transitory adaptive up-regulation of PD-L1 expression on CETCs.

Methods

CETCs and the expression of PD-L1 and Ki-67 were analyzed from 25 patients with primary non-metastatic breast cancer using the maintrac method. The fraction of PD-L1 and Ki-67 positive CETCs were assessed at baseline, 3 and 6 weeks after start of RT and 6 weeks after end of therapy. Additionally, copy number status of PD-L1 was determined using FISH.

Results

Fractionated-dose RT leads to a significant increase in PD-L1 expression on CETCs with the highest expression level midterm of irradiation as compared to baseline (49% vs. 74%, p < 0.01). 6 weeks after end of RT the number of PD-L1 positive CETCs returned to baseline value. The up-regulation of PD-L1 was dose dependent. Patients who received higher total dose had significantly more PD-L1 positive CETCs as compared to patients treated with lower total dose midterm of RT (64% vs. 43, p < 0.05). Before start of therapy there was a correlation between the fraction of PD-L1 and Ki-67 positive CETCs (r = 0.6, p < 0.01). PD-L1 copy number gains were significantly associated with PD-L1 expression (r = 0.6, P < 0.05).

Conclusions

RT leads to an up-regulation of PD-L1 expression on CETCs, which could be a possible mechanism of acquired radioresistance. Combining immunomodulatory agents with radiation might have the potential to overcome this resistance and could improve clinical outcome in breast cancer.

Clinical trial identification

Legal entity responsible for the study

Katharina Pachmann.

Funding

Has not received any funding.

Editorial Acknowledgement

Disclosure

All authors have declared no conflicts of interest.

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