ESTRO 2024 - Abstract Book

S5214

Radiobiology - Microenvironment

ESTRO 2024

Conclusion:

Taken together, our work demonstrates that hypoxia remodels the transcriptional and epigenetic landscape in GBM to adapt to hypoxic stress. In patients, hypoxia and the genes found within epigenetically regulated regions associate with specific phenotypic cell states potentially affecting cellular state differentiation and contributing to malignant phenotypes within tumours.

Keywords: glioblastoma, hypoxia, spatial transcriptomics

1638

Digital Poster

Investigating the effects of neo-adjuvant chemotherapy on the bladder cancer immune microenvironment

Mark Reardon 1 , Jamie Honeychurch 1 , Eleanor Cheadle 1 , Pedro Oliveira 2 , Kimberly Reeves 1 , Peter Hoskin 1 , Ananya Choudhury 1,3 , Richard Walshaw 4 1 University of Manchester, Division of Cancer Sciences, Manchester, United Kingdom. 2 The Christie NHS Foundation Trust, Department of Pathology, Manchester, United Kingdom. 3 The Christie NHS Foundation Trust, Department of Clinical Oncology, Manchester, United Kingdom. 4 The Clatterbridge Cancer Centre NHS Foundation Trust, Department of Clinical Oncology, Liverpool, United Kingdom

Purpose/Objective:

Patients with bladder cancer (BCa) are offered the choice of radical cystectomy or chemoradiotherapy (CRT), with similar survival outcomes. Cisplatin-based neo-adjuvant chemotherapy (NAC) is standard-of-care in the UK prior to these definitive treatments [1] . As cancers grow, a tumour microenvironment (TME) develops that contains anti tumour immune cells such as cytotoxic CD8+ T cells, but which also contains pro-tumour immune cells such as cancer-associated fibroblasts (CAFs) and regulatory T cells (T-regs). BCa patients whose tumours have high levels of immune infiltration have better survival outcomes after CRT but, while NAC can affect immune infiltration in some cancers, the effects of NAC on the TME in BCa have not been fully explored [2] . We hypothesise that targeting specific pro-tumour immune mechanisms improves patient responses to NAC in BCa.

Material/Methods:

An RNA-Seq differential gene expression analysis [3, 4] was performed on matched pre- and post-NAC tumour samples from a cohort of 32 BCa patients treated with 3 cycles of cisplatin-based NAC followed by radical cystectomy. Gene expression immune signatures curated from the literature were calculated and analysed in conjunction with clinical outcomes. Correlation analyses of pro- and anti-tumour signatures were performed to investigate BCa tumour resistance mechanisms to NAC.

Results: