• G Boulle, Y Velut, A Mansuet-Lupo, L Gibault, H Blons, L Fournel, A Boni, I Cremer, M Wislez, V Duchatelle, J Trédaniel, S A Hammond, R Herbst, M Alifano, P Giraud, and D Damotte.
• Institut National de La Santé et de La Recherche Médicale (INSERM), UMRS 1138, Cordeliers Research Center, Team Cancer, inflammation and complement, Paris, France; University Paris Descartes, Paris, France... more ; University Pierre et Marie Curie-Paris, Paris, France. less
• Eur. J. Cancer. 2020 Aug 1; 135: 221-229.

BackgroundRadiotherapy is a standard of care for locally advanced stage III N2 non-small-cell lung carcinoma (NSCLC) combined with surgery/chemotherapy. Radiotherapy is hypothesised to induce tumour immunogenic cell death, to release neoantigen resulting in intra-tumoural immune infiltration and abscopal effect. Conversely, it has not been demonstrated if immune cells are necessary to drive radiotherapy efficacy and predict patient's survival.Patients And MethodsWe retrospectively analysed tumour samples and clinical data from 113 patients, 89 resected (PORT) and 24 non-resected (DRC) N2-NSCLC treated with chemotherapy and radiotherapy (same radiotherapy department from 2002 to 2015). The immune environment was characterised with in situ multiplex staining (CD8, FoxP3, PD-L1 and cytokeratin) and correlated with clinical data and survival.ResultsHigh density of CD8+ T cells was associated with OS (p = 0.04, HR = 1.93 [0.99-3.78]) and DFS (p = 0.003, HR = 2.42 [1.31-4.47]) in the PORT. High density of CD8+/FoxP3+ double positive cells was associated with OS (p = 0.01, HR = 1.97 [1.11-3.48]) in the whole population, with OS (p = 0.05, HR = 1.92 [0.98-3.74]) and PFS (p = 0.03, HR = 1.83 [1.03-3.23]) in the PORT without reaching significance for the DRC. Intermediate PD-L1 expression in tumour cells (TPS = 1-49%) was associated with a higher survival in the PORT.ConclusionsIntra-tumoural CD8+ T cell and particularly CD8+/FoxP3+ double positive T cell densities predict survival in stage III N2-NSCLC suggesting the need for a pre-existing intra-tumour immunity to mediate the action of radiotherapy. Density of CD8+/FoxP3+ cells was the best predictor of patient's survival in multivariate analysis and could represent a biomarker of radiotherapy efficacy.Copyright © 2020 Elsevier Ltd. All rights reserved.

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