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Sams, L.; Kruger, S.; Heinemann, V.; Bararia, D.; Haebe, S.; Alig, S.; Haas, M.; Zhang, D.; Westphalen, C. B.; Ormanns, S.; Metzger, P.; Werner, J.; Weigert, O.; von Bergwelt-Baildon, M.; Rataj, F.; Kobold, S. und Boeck, S. (2021): Alterations in regulatory T cells and immune checkpoint molecules in pancreatic cancer patients receiving FOLFIRINOX or gemcitabine plus nab-paclitaxel. In: Clinical & translational oncology : official publication of the Federation of Spanish Oncology Societies and of the National Cancer Institute of Mexico [PDF, 1MB]

Abstract

PURPOSE This pilot study aimed on generating insight on alterations in circulating immune cells during the use of FOLFIRINOX 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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