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

Clin Transl Oncol. 2021 Nov;23(11):2394-2401. doi: 10.1007/s12094-021-02620-x. Epub 2021 Apr 19.

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.

Keywords: FOLFIRINOX; Gemcitabine; Immune checkpoints; Nab-paclitaxel; Pancreatic cancer; Regulatory T cells.

MeSH terms

  • Aged
  • Albumins / therapeutic use
  • Antineoplastic Combined Chemotherapy Protocols / therapeutic use*
  • CD4-Positive T-Lymphocytes / chemistry
  • CD4-Positive T-Lymphocytes / drug effects
  • CD8-Positive T-Lymphocytes / chemistry
  • CD8-Positive T-Lymphocytes / drug effects
  • Carcinoma, Pancreatic Ductal / drug therapy*
  • Carcinoma, Pancreatic Ductal / immunology
  • Deoxycytidine / analogs & derivatives
  • Deoxycytidine / therapeutic use
  • Female
  • Fluorouracil / therapeutic use
  • Forkhead Transcription Factors
  • Gemcitabine
  • Hepatitis A Virus Cellular Receptor 2 / analysis
  • Humans
  • Immune Checkpoint Proteins / analysis
  • Immune Checkpoint Proteins / drug effects*
  • Irinotecan / therapeutic use
  • Leucovorin / therapeutic use
  • Male
  • Middle Aged
  • Oxaliplatin / therapeutic use
  • Paclitaxel / therapeutic use
  • Pancreatic Neoplasms / drug therapy*
  • Pancreatic Neoplasms / immunology
  • Pilot Projects
  • Programmed Cell Death 1 Receptor / analysis
  • Programmed Cell Death 1 Receptor / drug effects
  • Progression-Free Survival
  • Prospective Studies
  • T-Lymphocytes, Regulatory / chemistry
  • T-Lymphocytes, Regulatory / drug effects*

Substances

  • 130-nm albumin-bound paclitaxel
  • Albumins
  • FOXP3 protein, human
  • Forkhead Transcription Factors
  • HAVCR2 protein, human
  • Hepatitis A Virus Cellular Receptor 2
  • Immune Checkpoint Proteins
  • PDCD1 protein, human
  • Programmed Cell Death 1 Receptor
  • folfirinox
  • Oxaliplatin
  • Deoxycytidine
  • Irinotecan
  • Paclitaxel
  • Leucovorin
  • Fluorouracil
  • Gemcitabine