Stereotactic ablative radiotherapy (SABR) has been succesfully used in patients with medically inoperable non-small cell lung cancer (NSCLC). High physical doses of radiotherapy translate into extremely high biological doses more effective in tumor control. Other mechanisms including immune are also postulated.
The aim of our study was to prospectively assess the effect of high dose ionizing radiation of the lung tumor on changes in the expression of peripheral T cell activation markers (AM) – CTLA-4, PD-1 and transcription factors (TF) associated with Th1, Th2, Th17 and regulatory T cell subpopulations (T-bet, GATA-3, ROR-yt, Fox-P3) and secretion of characteristic cytokines.
In patients with previously untreated NSCLC in stage T1-2aN0M0 receiving SABR peripheral blood mononuclear cells (PBMC) and blood serum was drawn three times - before 1 fraction (D1), two weeks (D2) and 3 months (D3) after radiotherapy. Expression level of selected AM, TF and cytokines was measured by flow cytometry.
From September 2013 to March 2016 we enrolled 94 patients aged 53 to 87 years (median 74 years). All patients underwent SABR in accordance with local standards. The D1, D2 and D3 control points were achieved by 92, 92 and 79 patients, respectively. A significant increase in the fraction of CD4+ and CD8+ T-cells with expression of PD-1 and CTLA-4 AM was found in all patients at D2 and D3 control points. Additionally increased level of Th1, Th2 and Th17 type of CD4+ T cells (T-bet, GATA-3, ROR-yt positive, respectively), and a reduction of T-reg - Fox-P3 (+) fraction with simultaneous elevation of Th1 (Il12, INF-y), Th2 (Il-4, Il-13) and Th17 (Il17) cytokines was also detected at D2 and D3 control points.
In patients with early NSCLC, enhanced expression of AM after SABR suggests the activation of CD4+ and CD8+ T-cells. These changes correlate with stimulation of Th1, Th2 and Th17 type systemic immune response and reduction of the number of T-reg cells. The project was financed by the Polish National Science Centre, Grant no UMO-2012/07/B/NZ5/00587.
Clinical trial identification
Legal entity responsible for the study
Medical University of Gdansk
Polish National Science Centre, Grant no UMO-2012/07/B/NZ5/00587.
R. Zaucha: Travel grants from Amgen, Roche, MSD, BMS. Educational grants from Roche, MSD, Nutricia. All above were not connected to presented reserch. All other authors have declared no conflicts of interest.