ESTRO 2024 - Abstract Book

S5313

Radiobiology - Tumour biology

ESTRO 2024

Interestingly, humoral immune response was consistently affected before and during treatment in our GO enrichment analysis, suggesting hypoxia influences radiotherapy modulation of the immune response. A candidate 3-protein plasma signature (fold change>2, p. adj.<0.01, before radiotherapy) was derived that correlated with the 24 gene hypoxia signature (R=0.67, p=0.015). All three proteins [PH1] from the signature were consistently upregulated during radiotherapy in patients with hypoxic bladder cancers. Hierarchical, PCA and k-means clustering analyses showed the candidate 3-protein signature also mimicked the patient stratification obtained using the 24-gene signature.

Conclusion:

Effects of tumour hypoxia on the plasma proteome are time-dependent, as it affects ECM remodelling and coagulation pathways only before and during the first weeks of radiotherapy. However, hypoxia-induced changes in the plasma proteome were consistently associated with humoral immune response pathways both before and during radiotherapy, suggesting it modulates bladder cancer patient’s immune-response before and during standard-of-care treatment. Finally, a candidate 3-protein plasma hypoxia signature was identified. To the best of our knowledge, this is the first serial proteomic plasma profiling of patients linked with tumour hypoxia. Future studies should evaluate the potential benefit of hypoxia-modifying treatment together with immunotherapy (e.g. anti PD-1/PD-L1 inhibition), as well as perform prospective validation of the proposed plasma hypoxia signature.

Keywords: Biomarkers; hypoxia; proteomics

References:

1. Hoskin, P. J., Sibtain, A., Daley, F. M. & Wilson, G. D. GLUT1 and CAIX as intrinsic markers of hypoxia in bladder cancer: relationship with vascularity and proliferation as predictors of outcome of ARCON. Br J Cancer 89, 1290–1297 (2003).

2. Yang, L. et al. A Gene Signature for Selecting Benefit from Hypoxia Modification of Radiotherapy for High-Risk Bladder Cancer Patients. Clinical Cancer Research 23, 4761–4768 (2017).

3. Hadjidemetriou, M. et al. Nano-scavengers for blood biomarker discovery in ovarian carcinoma. Nano Today 34, 100901 (2020).

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Digital Poster

Development of chemoradiation therapy targeting EGFR for triple negative breast cancer.

Takamitsu Hara 1 , Tomoo Funayama 2 , Tatsuya Ohno 3 , Yoshihiro Nakagami 4 , Yoshiyuki Suzuki 5

1 Gunma Prefectural College of Health Sciences, Radiological Technology, Maebashi, Japan. 2 National Institutes for Quantum and Radiological Science and Technology, Takasaki Advanced Radiation Research Institute, Takasaki, Japan.