Testoni Sabrina Gloria Giulia, Minici Claudia, Benetti Elisa, Clemente Francesca, Boselli Daniela, Sciorati Clara, De Monte Lucia, Petrone Maria Chiara, Enderle Markus, Linzenbold Walter, Protti Maria Pia, Manfredi Angelo, De Cobelli Francesco, Reni Michele, Falconi Massimo, Capurso Gabriele, Arcidiacono Paolo Giorgio, Della-Torre Emanuel
Pancreatico-Biliary Endoscopy and Endosonography Division, Pancreas Translational & Clinical Research Center, IRCCS San Raffaele Scientific Institute, Vita-Salute San Raffaele University, Via Olgettina 60, 20132 Milan, Italy.
IRCCS San Raffaele Scientific Institute, Vita-Salute San Raffaele University, Via Olgettina 60, 20132 Milan, Italy.
Cancers (Basel). 2023 Jul 21;15(14):3704. doi: 10.3390/cancers15143704.
Immunological consequences of endoscopic ultrasound (EUS)-local thermal ablation (LTA) for pancreatic ductal adenocarcinoma (PDAC) have not been extensively assessed. We aimed to explore EUS-LTA effects on the systemic immune response in PDAC. Peripheral blood was collected from 10 treatment-naïve patients with borderline resectable and locally advanced PDAC, randomly allocated to Nab-paclitaxel plus Gemcitabine chemotherapy (CT-arm, n = 5) or EUS-LTA with HybridTherm Probe plus CT (HTP + CT-arm, n = 5). Twenty healthy donors were included as controls. Flow-cytometry and multiplex assays were used to profile immune cell subsets and measure serum cytokines/chemokines, respectively. At baseline, PDAC patients showed increased circulating monocytes and lower circulating lymphocytes and CD19+ B cells counts compared to healthy controls. After 4 months, CT induced decrease of B regulatory cells, CD4+ cytotoxic T cells and IL-1β. The addition of EUS-HTP to CT selectively decreased the serum levels of APRIL/TNFSF13 as well as T regulatory cells, total, classic and inflammatory monocytes. Serum levels of APRIL/TNFSF13 and total, classic and inflammatory monocytes counts at baseline were associated with worse overall survival. EUS-HTP has the potential to selectively impact on immune cells and cytokines associated with poor outcomes in PDAC.
内镜超声(EUS)局部热消融(LTA)治疗胰腺导管腺癌(PDAC)的免疫后果尚未得到广泛评估。我们旨在探讨EUS-LTA对PDAC全身免疫反应的影响。收集了10例未经治疗的临界可切除和局部晚期PDAC患者的外周血,这些患者被随机分配接受纳武单抗联合吉西他滨化疗(CT组,n = 5)或EUS-LTA联合HybridTherm探头加CT(HTP + CT组,n = 5)。纳入20名健康供者作为对照。分别使用流式细胞术和多重检测来分析免疫细胞亚群并测量血清细胞因子/趋化因子。在基线时,与健康对照相比,PDAC患者循环单核细胞增加,循环淋巴细胞和CD19 + B细胞计数降低。4个月后,CT导致B调节细胞、CD4 + 细胞毒性T细胞和IL-1β减少。在CT基础上加用EUS-HTP可选择性降低血清APRIL/TNFSF13水平以及调节性T细胞、总单核细胞、经典单核细胞和炎性单核细胞水平。基线时血清APRIL/TNFSF13水平以及总单核细胞、经典单核细胞和炎性单核细胞计数与较差的总生存期相关。EUS-HTP有可能选择性影响与PDAC不良预后相关的免疫细胞和细胞因子。