Immunological responses to brain metastasis stereotactic radiosurgery in patient-matched longitudinal blood and tumour samples
- Author(s)
- Sia, J; D'Souza, C; Castle, B; Huang, YK; Aw Yeang, HX; Idrizi, R; Jana, M; Siva, S; Phillips, C; Neeson, P;
- Journal Title
- Clinical and Translational Radiation Oncology
- Publication Type
- Research article
- Abstract
- BACKGROUND: Stereotactic radiosurgery (SRS) is highly effective as focal treatment for brain metastases (BrMs), but whether it can promote anti-tumour immune responses that synergise with immunotherapy remains unclear. We investigated this by examining blood samples from a clinical trial for HER2-amplified breast cancer (HER2-BC) BrMs, matched with longitudinal HER2-BC BrM samples resected from the same location in the same patient. METHODS: Blood samples from 10 patients taken pre- and 7-14 days post-SRS were analysed by mass and flow cytometry. One patient received pre-operative SRS for a BrM that recurred 7 months after resection, followed by planned re-resection 8 days post-SRS. Pre- and post-SRS tumours from this patient were analysed by bulk RNAseq, multiplex immunohistochemistry (mIHC), and TCR sequencing. RESULTS: Monocytes, central memory CD8+ T and regulatory T cells were enriched in blood post-SRS, together with increased MHC-II expression on monocytes, conventional DCs, and monocytic MDSCs. In tumour, SRS upregulated antigen presentation, T cell proliferation and T cell co-stimulation signatures, alongside an influx of tumour-associated macrophages (TAMs) and CD4+ T cells. Specifically, TAMs and CD4+ T cells, but not CD8+ T cells, demonstrated spatial co-localisation post-SRS. These TAMs were lowly PD-L1 expressing, but CD4+ T cells showed increased PD-1 expression. A sizeable proportion of T cell clonotypes were retained post-SRS, and four clones demonstrated significant, non-stochastic expansion. CONCLUSION: Systemic and local immunological changes in this homogenous patient cohort suggest that SRS may facilitate MHC-II-restricted T cell priming responses involving the monocyte-macrophage lineage and CD4+ T cells, which should be further explored.
- Publisher
- Elsevier
- Keywords
- Brain metastases; Radiotherapy; Stereotactic radiation therapy; Tumour immunology
- Department(s)
- Radiation Oncology; Laboratory Research
- Publisher's Version
- https://doi.org/10.1016/j.ctro.2024.100863
- Terms of Use/Rights Notice
- Refer to copyright notice on published article.
Creation Date: 2024-11-07 06:46:47
Last Modified: 2024-11-07 06:54:52