Tumour radiosensitivity is associated with immune activation in solid tumours
Purpose Our goal was to determine whether tumour radiosensitivity is associated with activation of the immune system across all tumour types as measured by two gene expression signatures (GESs). Methods We identified 10,240 genomically profiled distinct solid primary tumours with gene expression analysis available from an institutional de-identified database. Two separate GESs were included in the analysis, the radiosensitivity index (RSI) GES (a 10-gene GES as a measure of radiosensitivity) and the 12-chemokine (12-CK) signature (a 12-gene GES as a measure of immune activation). We tested whether the RSI and 12-CK were associated with each other across all tumour samples and, in an exploratory analysis, their prognostic significance in predicting distant metastasis-free survival (DMFS) among a well-characterised, independent cohort of 282 early-stage breast cancer cases treated with surgery and post-operative radiation alone without systemic therapy. The lower the RSI score, the higher the tumour radiosensitivity; whereas, the higher the 12-CK score the higher the immune activation. Results Using an RSI cut-point of ≤0.3745, RSI-low tumours (n = 4,291, 41.9%) had a significantly higher median 12-CK GES value (0.54 [−0.136, 1.095]) compared with RSI-high tumours (−0.17 [–0.82, 0.42]; p < 0.001) across all tumour samples, indicating that radiosensitivity is associated with immune activation. In an exploratory analysis of early-stage breast cancer cases, a multivariable model with patient age, RSI and 12-CK provided a strong composite model for DMFS (p = 0.02), with RSI (hazard ratio [HR] 0.63 [95% confidence interval 0.36, 1.09]) and 12-CK (HR 0.66 [0.41, 1.04]) each providing comparable contributions. Conclusions Tumour radiosensitivity is associated with immune activation as measured by the two GESs.
|Keywords||Cancer, Immune, Radiation, Radiosensitivity, Survival|
|Persistent URL||dx.doi.org/10.1016/j.ejca.2017.08.001, hdl.handle.net/1765/101653|
|Journal||European Journal of Cancer|
Strom, T. (Tobin), Harrison, L.B. (Louis B.), Giuliano, A.R. (Anna R.), Schell, M.J. (Michael J.), Eschrich, S.A, Berglund, A. (Anders), … Torres-Roca, J.F. (2017). Tumour radiosensitivity is associated with immune activation in solid tumours. European Journal of Cancer, 84, 304–314. doi:10.1016/j.ejca.2017.08.001