Resumen de Alterations in regulatory T cells and immune checkpoint molecules in pancreatic cancer patients receiving FOLFIRINOX or gemcitabine plus nab‑paclitaxel
L. Sams, S. Kruger, V. Heinemann, D. Bararia, S. Haebe, S. Alig, M. Haas, D. Zhang, C. B. Westphalen, S. Ormanns, P. Metzger, J. Werner, O. Weigert, Michael S. von Bergwelt Baildon, F. Rataj
Purpose This pilot study aimed on generating insight on alterations in circulating immune cells during the use of FOL- FIRINOX and gemcitabine/nab-paclitaxel in pancreatic ductal adenocarcinoma (PDAC).
Patients and methods Peripheral blood mononuclear cells were isolated before and 30 days after initiation of chemotherapy from 20 patients with advanced PDAC. Regulatory T cells (FoxP3+) and immune checkpoints (PD-1 and TIM-3) were analyzed by flow cytometry and immunological changes were correlated with clinical outcome.
Results Heterogeneous changes during chemotherapy were observed in circulating T-cell subpopulations with a pronounced effect on PD-1+ CD4+/CD8+ T cells. An increase in FoxP3+ or PD-1+ T cells had no significant effect on survival. An increase in TIM3+/CD8+ (but not TIM3+/CD4+) T cells was associated with a significant inferior outcome: median progression-free survival in the subgroup with an increase of TIM-3+/CD8+ T cells was 6.0 compared to 14.0 months in patients with a decrease/no change (p = 0.026); corresponding median overall survival was 13.0 and 20.0 months (p = 0.011), respectively.
Conclusions Chemotherapy with FOLFIRNOX or gemcitabine/nab-paclitaxel induces variable changes in circulating T-cell populations that may provide prognostic information in PDAC
