Clinical & translational oncology : official publication of the Federation of Spanish Oncology Societies and of the National Cancer Institute of Mexico · 2021
Alterations in regulatory T cells and immune checkpoint molecules in pancreatic cancer patients receiving FOLFIRINOX or gemcitabine plus nab-paclitaxel.
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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, Boeck S
Аннотация
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.
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.
Предметные рубрики MeSH
AgedAlbuminsAntineoplastic Combined Chemotherapy ProtocolsCD4-Positive T-LymphocytesCD8-Positive T-LymphocytesCarcinoma, Pancreatic DuctalDeoxycytidineFemaleFluorouracilForkhead Transcription FactorsHepatitis A Virus Cellular Receptor 2HumansImmune Checkpoint ProteinsIrinotecanLeucovorinMaleMiddle AgedOxaliplatinPaclitaxelPancreatic NeoplasmsPilot ProjectsProgrammed Cell Death 1 ReceptorProgression-Free SurvivalProspective StudiesT-Lymphocytes, RegulatoryGemcitabine