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

C B Westphalen, S Boeck, S Kobold, F Rataj, M von Bergwelt-Baildon, O Weigert, J Werner, P Metzger, S Ormanns, L Sams, D Zhang, M Haas, S Alig, S Haebe, D Bararia, V Heinemann, S Kruger

Journal: Clinical & translational oncology : official publication of the Federation of Spanish Oncology Societies and of the National Cancer Institute of Mexico 2022;23(11):2394-2401

PMID: 33876417

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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.

Address: Department of Internal Medicine III and Comprehensive Cancer Center, Grosshadern University Hospital, Ludwig-Maximilians-University of Munich, Marchioninistr. 15, 81377, Munich, Germany.; German Cancer Consortium (DKTK), Partner Site Munich, Munich, Germany.; Laboratory for Experimental Leukemia and Lymphoma Research (ELLF), Department of Internal Medicine III, Grosshadern University Hospital, Ludwig-Maximilians-University, Munich, Germany.; Institute of Pathology, Faculty of Medicine, Ludwig-Maximilians-University, Munich, Germany.; Center of Integrated Protein Science Munich (CIPS-M) and Division of Clinical Pharmacology, University Hospital of the Ludwig-Maximilians-University, Munich, Germany.; Department of General, Visceral and Transplantation Surgery, Ludwig-Maximilians-University, Munich, Germany.; Department of Internal Medicine III and Comprehensive Cancer Center, Grosshadern University Hospital, Ludwig-Maximilians-University of Munich, Marchioninistr. 15, 81377, Munich, Germany. [email protected].; German Cancer Consortium (DKTK), Partner Site Munich, Munich, Germany. [email protected].

DOI: 10.1007/s12094-021-02620-x