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
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