Concurrent and sequential
cisplatin-based
chemoradiotherapy regimens are standard therapeutic approaches in
cancer treatment. Recent clinical data suggest that these different dosing schedules may adversely affect
antigen-specific
immunotherapy. The goal of the present preclinical study was to explore the effects of concurrent and sequential
cisplatin/
radiotherapy on immune status in a
lung cancer mouse model. A total of 150 C57BL/6 mice were randomized into six treatment groups: control; 8 Gy thoracic
radiotherapy (dose schedules 1 and 2);
cisplatin 2.5 mg/kg i.p.;
cisplatin +
radiotherapy (concurrent); and
cisplatin +
radiotherapy (sequential; n = 25, all groups). At the end of the study (week 41), serum
cytokines were assessed by multiplex immunoassay, surface markers of spleen-derived lymphocytes were assessed by immunostaining and flow cytometry, lung
tumor expression of programmed death
ligands 1 and 2 (PD-L1/2) was evaluated by immunohistochemistry, and
miRNA profiling was performed in serum and lymphocytes by quantitative real-time PCR. Lung whole mounts were prepared to assess treatment effects on lung
tumor foci formation. The results showed that sequential
chemoradiotherapy (two cycles of
cisplatin followed by 8 Gy
radiotherapy) had equivalent antitumor activity as concurrent
therapy. However, sequential
cisplatin/
radiotherapy resulted in significant differences in several immune response
biomarkers, including regulatory T cells, miR-29c, expression of costimulatory molecule CD28, and serum IFNγ. PD-L1 and PD-L2 were strongly expressed in
tumor foci, but no trend was seen between groups. These results suggest that monitoring immune status may be necessary when designing treatment regimens combining
immunotherapy with
chemoradiotherapy.