Neoadjuvant FOLFIRINOX Therapy Is Associated with Increased Effector T Cells and Reduced Suppressor Cells in Patients with Pancreatic Cancer.
Neoadjuvant FOLFIRINOX Therapy Is Associated with Increased Effector T Cells and Reduced Suppressor Cells in Patients with Pancreatic Cancer.
复制标题
新辅助FOLFIRINOX治疗与胰腺癌患者效应T细胞增加和抑制细胞减少相关。
DOI：
10.1158/1078-0432.ccr-21-0998
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发表时间：
2021-12-15
期刊：
影响因子：
--
通讯作者：
Hawkins WG
中科院分区：
文献类型：
--
作者：
Peng H;James CA;Cullinan DR;Hogg GD;Mudd JL;Zuo C;Takchi R;Caldwell KE;Liu J;DeNardo DG;Fields RC;Gillanders WE;Goedegebuure SP;Hawkins WG
FOLFIRINOX已被证明对胰腺导管腺癌(PDAC)患者有良好的疗效。化疗诱导的免疫原性细胞死亡可以激发抗肿瘤免疫反应。因此，我们对外周血中的免疫细胞亚群进行了高维分析，以评估FOLFIRINOX对免疫系统的影响。20例初治和19例接受FOLFIRINOX治疗的原发性PDAC肿瘤患者在手术切除时采集外周血单个核细胞(PBMC)。采用飞行时间质谱仪(CyTOF)对PBMC进行36种标志物的鉴定。与单纯治疗的患者相比，FOLFIRINOX治疗的患者表现出明显的免疫特征，包括炎性单核细胞和调节性T细胞(Treg)显著减少，Th1细胞增加，Th2细胞减少。值得注意的是，单核细胞和Treg都表达高水平的免疫抑制相关的CD39，而接受FOLFIRINOX治疗的患者的CD39+细胞总数明显低于未治疗的患者。在FOLFIRINOX应答者中观察到的细胞变化包括Treg频率显著降低，总CD8T细胞频率增加，CD27CD4Tbet+效应/效应记忆亚群−和CD8T细胞频率增加。我们的研究表明，FOLFIRINOX的新辅助化疗增强了效应T细胞，下调了抑制细胞。这些数据表明，FOLFIRINOX新辅助治疗可以改善PDAC患者的免疫治疗和临床结果。
FOLFIRINOX has demonstrated promising results for patients with pancreatic ductal adenocarcinoma (PDAC). Chemotherapy-induced immunogenic cell death can prime antitumor immune responses. We therefore performed high-dimensional profiling of immune cell subsets in peripheral blood to evaluate the impact of FOLFIRINOX on the immune system. Peripheral blood mononuclear cells (PBMC) were obtained from treatment-naïve (n = 20) and FOLFIRINOX-treated patients (n = 19) with primary PDAC tumors at the time of resection. PBMCs were characterized by 36 markers using mass cytometry by time of flight (CyTOF). Compared with treatment-naïve patients, FOLFIRINOX-treated patients showed distinct immune profiles, including significantly decreased inflammatory monocytes and regulatory T cells (Treg), increased Th1 cells, and decreased Th2 cells. Notably, both monocytes and Treg expressed high levels of immune suppression-associated CD39, and the total CD39+ cell population was significantly lower in FOLFIRINOX-treated patients compared with untreated patients. Cellular alterations observed in responders to FOLFIRINOX included a significantly decreased frequency of Treg, an increased frequency of total CD8 T cells, and an increased frequency of CD27−Tbet+ effector/effector memory subsets of CD4 and CD8 T cells. Our study reveals that neoadjuvant chemotherapy with FOLFIRINOX enhances effector T cells and downregulates suppressor cells. These data indicate that FOLFIRINOX neoadjuvant therapy may improve immune therapy and clinical outcome in patients with PDAC.
影响因子：
3
作者：
Rahman SH;Urquhart R;Molinari M
通讯作者：
Molinari M