ESTRO 2024 - Abstract Book

S5215

Radiobiology - Microenvironment

ESTRO 2024

Significantly over-expressed genes were enriched inter alia for immune signalling, cell cycle, proliferation and response to hypoxia, demonstrating heterogeneous BCa responses to NAC. Seven tumours had low immune infiltration after NAC while 25 had high post-NAC infiltration of both pro- and anti-tumour immune cells. The consensus subtypes [5] of tumours which did not regress after NAC were nevertheless shifted further towards immune-infiltrated stroma-rich and basal/squamous subtypes. Changes in the CD8+ T cell signature in muscle invasive tumours were mirrored closely by the exhausted CD8 signature (Pearson’s r = 0.80, p = 1.7 x 10 -6 ), suggesting that the CD8+ T cells recruited into the TME were inactive in these tumours. Significant proportional changes for some pro-tumour signatures, such as T-regs (r = 0.56, p = 3.5 x 10 -3 ) and immune checkpoints (r = 0.71, p = 6.7 x 10 -5 ) were seen, but not for others such as CAFs or M2 macrophages.

Conclusion:

Partial responders are ’immune-cold’, consistent with previously demonstrated increase and subsequent decrease of immune expression post-NAC [6] . Non-responder tumour subtypes were also shifted further towards immune-infiltrated. Our data suggest that the presence of T-regs or expression of immune checkpoints could be associated with the response of BCa to NAC, with a subset of non-responders remaining ‘immune-hot’ after treatment [7] . Validation analyses are ongoing in a number of external datasets.

Keywords: immune infiltration

References:

1. National Collaborating Centre for Cancer. National Institute for Health and Clinical Excellence: Guidance, Bladder Cancer: Diagnosis and Management. 2015.

2. Galluzzi, L., et al., Immunostimulation with chemotherapy in the era of immune checkpoint inhibitors. Nat Rev Clin Oncol, 2020. 17(12): p. 725-741.

3. Dobin, A., et al., STAR: ultrafast universal RNA-seq aligner. Bioinformatics, 2013. 29(1): p. 15-21.

4. Love, M.I., W. Huber, and S. Anders, Moderated estimation of fold change and dispersion for RNA-seq data with DESeq2. Genome Biol, 2014. 15(12): p. 550.

5. Kamoun, A., et al., A Consensus Molecular Classification of Muscle-invasive Bladder Cancer. Eur Urol, 2020. 77(4): p. 420-433.

6. Park, Y.H., et al., Chemotherapy induces dynamic immune responses in breast cancers that impact treatment outcome. Nat Commun, 2020. 11(1): p. 6175.

7. Seiler, R., et al., Divergent Biological Response to Neoadjuvant Chemotherapy in Muscle-invasive Bladder Cancer. Clin Cancer Res, 2019. 25(16): p. 5082-5093.

1678

Digital Poster

Effect of irradiation on Head and Neck Squamous Cell Carcinoma-derived CAF phenotype and function.