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接受 FOLFIRINOX 或吉西他滨加 nab-紫杉醇治疗的胰腺癌患者调节性 T 细胞和免疫检查点分子的改变。

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

机构信息

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.

出版信息

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

DOI:10.1007/s12094-021-02620-x
PMID:33876417
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC8455387/
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.

摘要

目的

本研究旨在探讨在使用 FOLFIRINOX 和吉西他滨/白蛋白紫杉醇治疗胰腺导管腺癌（PDAC）期间循环免疫细胞的变化。

患者和方法

从 20 名晚期 PDAC 患者中，在开始化疗前和 30 天后分离外周血单核细胞。通过流式细胞术分析调节性 T 细胞（FoxP3+）和免疫检查点（PD-1 和 TIM-3），并将免疫变化与临床结果相关联。

结果

在循环 T 细胞亚群中观察到化疗期间存在异质性变化，对 PD-1+CD4+/CD8+T 细胞的影响尤为显著。FoxP3+或 PD-1+T 细胞的增加对生存没有显著影响。TIM3+/CD8+（但不是 TIM3+/CD4+）T 细胞的增加与预后显著相关：TIM-3+/CD8+T 细胞增加亚组的无进展生存期中位数为 6.0 个月，而降低/无变化的患者为 14.0 个月（p=0.026）；相应的总生存期中位数分别为 13.0 和 20.0 个月（p=0.011）。

结论

FOLFIRINOX 或吉西他滨/白蛋白紫杉醇化疗诱导循环 T 细胞群的变化，可能为 PDAC 提供预后信息。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0379/8455387/64ab7fa7c18a/12094_2021_2620_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0379/8455387/50a4c234371e/12094_2021_2620_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0379/8455387/c81c82b7505b/12094_2021_2620_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0379/8455387/0cd05aec8aec/12094_2021_2620_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0379/8455387/64ab7fa7c18a/12094_2021_2620_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0379/8455387/50a4c234371e/12094_2021_2620_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0379/8455387/c81c82b7505b/12094_2021_2620_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0379/8455387/0cd05aec8aec/12094_2021_2620_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0379/8455387/64ab7fa7c18a/12094_2021_2620_Fig4_HTML.jpg

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