Alterations in regulatory T cells and immune checkpoint molecules in pancreatic cancer patients receiving FOLFIRINOX or gemcitabine plus nab‑paclitaxel

• L. Sams ^[1] ; S. Kruger ^[1] ; V. Heinemann ^[1] ; D. Bararia ^[1] ; S. Haebe ^[1] ; S. Alig ^[1] ; M. Haas ^[1] ; D. Zhang ^[1] ; C. B. Westphalen ^[1] ; S. Ormanns ^[2] ; P. Metzger ^[3] ; J. Werner ^[4] ; O. Weigert ^[1] ; M. von Bergwelt Baildon ^[1] ; F. Rataj ^[3]
  1. [1] Department of Internal Medicine III and Comprehensive Cancer Center, Grosshadern University Hospital, Ludwig- Maximilians-University of Munich, Marchioninistr. 15, 81377 Munich, Germany
  2. [2] Institute of Pathology, Faculty of Medicine, Ludwig-Maximil ians-University, Munich, Germany
  3. [3] Center of Integrated Protein Science Munich (CIPS-M) and Division of Clinical Pharmacology, University Hospital of the Ludwig-Maximilians-University, Munich, Germany
  4. [4] Department of General, Visceral and Transplantation Surgery, Ludwig-Maximilians-University, Munich, Germany

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• Localización: Clinical & translational oncology, ISSN 1699-048X, Vol. 23, Nº. 11, 2021, págs. 2394-2401
• Idioma: inglés
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  • 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