Evaluating the immunological effects of stereotactic ablative radiotherapy in patients with primary and oligometastatic cancer

Reed, Hannah 2024. Evaluating the immunological effects of stereotactic ablative radiotherapy in patients with primary and oligometastatic cancer. MD Thesis, Cardiff University. Item availability restricted.

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Abstract

The impact of radiotherapy (RT) on immune responses remains uncertain with reports of both immune-suppressive and -stimulatory effects. Findings from studies using animal models have shown hypofractionated RT can trigger an adaptive immune response. This thesis presents the findings of an observational study entitled, “Immune Responses in Stereotactic Ablative Body Radiotherapy (SABR) In primary and oligomeTatstatic cancer” The study was designed to examine the impact of SABR on immune cell populations in blood and T cell responses to cancer antigens and common virus-derived antigens. Thirty-one patients underwent blood sampling longitudinally during their SABR treatment. Peripheral blood mononuclear cells were isolated, T cells characterised by flow cytometry and ex vivo interferon-gamma ELISpots measured T cell responses to different tumour-associated and viral antigens. An increase in the neutrophil-to-lymphocyte-ratio (NLR) during SABR was a poor prognostic marker; the median progression-free survival (PFS) was 8 months in the group with an NLR increase ≥ 10% and the median PFS remained undefined in the group with a stable NLR (<10% increase or decrease) (p=0.0009). Lymphopenia post-SABR varied by radiation site, affecting lung or liver but not bone or lymph node sites. SABR did not drive changes in the proportions of T cell subsets or PD-1 expression on T cells in peripheral blood. Although Tregs rose in the 5 weeks after completion of SABR to bone metastasis, this was not observed for tumours in other locations. T cell responses to common viral antigens were diminished during RT, possibly due to RT-induced lymphopenia. T cell responses to a panel of tumour-associated antigens remained unchanged. The findings of this study point to an immunosuppressive effect of SABR. NLR rise during SABR is a poor prognostic marker, warranting further validation. Additional work is needed to identify mechanisms to preserve lymphocytes and improve outcomes for patients.

Item Type:	Thesis (MD)
Date Type:	Completion
Status:	Unpublished
Schools:	Medicine
Subjects:	R Medicine > R Medicine (General)
Date of First Compliant Deposit:	23 May 2024
Last Modified:	23 May 2024 15:34
URI:	https://orca.cardiff.ac.uk/id/eprint/169121

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