研究动态
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胰腺癌患者新辅助治疗后的免疫微环境与首次手术相比的研究

The immune microenvironment after neoadjuvant therapy compared to upfront surgery in patients with pancreatic cancer.

发表日期:2023 Aug 17
作者: Eline S Zwart, Thomas van Ee, Deesje Doppenberg, Arantza Farina, Johanna W Wilmink, Eva Versteijne, Olivier R Busch, Marc G Besselink, Laura L Meijer, Yvette van Kooyk, Reina E Mebius, Geert Kazemier
来源: Cellular & Molecular Immunology

摘要:

手术前可切除性和边缘可切除性胰导管腺癌患者越来越多地在手术前接受新辅助治疗。然而,新辅助治疗对免疫微环境的影响仍然大部分未知。我们分析了接受新辅助治疗的胰腺癌肿瘤组织样本中的免疫微环境,与一次性手术后的患者进行比较,以了解治疗后的免疫环境。我们对接受一次性手术(n=10)、新辅助FOLFIRINOX(n=10)或吉西他滨+放疗(gem-RT)(n=9)后手术的胰腺导管腺癌患者的切除标本进行了多光谱成像。样本由专注于胰腺病理学的病理学家从肿瘤的中心部分和浸润前沿(通过切除的静脉或静脉表面)中选择,并通过Vectra Polaris进行分析。相比于接受新辅助gem-RT或一次性手术的患者,接受新辅助FOLFIRINOX的患者在肿瘤组织中显示出更多的调节性T细胞和更多的CD8 T细胞,表现出更多的促炎免疫特征。此外,在接受新辅助FOLFIRINOX的患者中,CD163+巨噬细胞数量减少,CD163-巨噬细胞与CD163+巨噬细胞比例更高。在所有治疗组中,肿瘤组织中的FoxP3+ B细胞百分比显著高于邻近组织。此外,在进行一次性手术或接受新辅助gem-RT的患者中,肿瘤组织中调节性T细胞数量增加。在接受新辅助gem-RT的组中,肿瘤组织中CD8 T细胞减少,CD163+巨噬细胞与CD8的比例增加,表明肿瘤组织中存在更强的免疫抑制特征。接受新辅助FOLFIRINOX的患者与接受新辅助gem-RT或进行一次性手术的患者相比,显示出更多的促炎免疫特征。此外,在所有治疗组中,与邻近非肿瘤组织相比,肿瘤组织中存在更强的免疫抑制微环境。 © 2023. 作者。
Patients with resectable and borderline resectable pancreatic ductal adenocarcinoma increasingly receive neoadjuvant therapy prior to surgery. However, the effect of neoadjuvant therapy on the immune microenvironment remains largely unknown. We analyzed the immune microenvironment in pancreatic cancer tumor tissue samples from patients treated with neoadjuvant therapy compared to patients after upfront surgery to gain knowledge about the immunological environment after therapy.Multispectral imaging was performed on tissue from resected specimens from patients with PDAC who underwent upfront surgery (n = 10), neoadjuvant FOLFIRINOX (n = 10) or gemcitabine + radiotherapy (gem-RT) (n = 9) followed by surgery. The samples were selected by a dedicated pancreas pathologist from both the central part and the invasive front of the tumor (by the resected vein or venous surface) and subsequently analyzed using the Vectra Polaris.Patients receiving neoadjuvant FOLFIRINOX display a more pro-inflammatory immune profile, with less regulatory T cells and more CD8 T cells in the tumor tissue compared to patients receiving neoadjuvant gem-RTgem-RT or undergoing upfront surgery. Furthermore, CD163+ macrophages were decreased, and a higher CD163- macrophages versus CD163+ macrophages ratio was found in patients with neoadjuvant FOLFIRINOX. In all treatment groups, percentage of FoxP3+ B cells was significantly higher in tumor tissue compared to adjacent tissue. Furthermore, an increase in regulatory T cells in the tumor tissue was found in patients undergoing upfront surgery or receiving neoadjuvant gem-RT. In the gem-RT group, less CD8 T cells and a higher CD163+ macrophages to CD8 ratio were noted in the tumor tissue, suggesting a more immune suppressive profile in the tumor tissue.Patients receiving neoadjuvant FOLFIRINOX display a more pro-inflammatory immune profile compared to patients receiving neoadjuvant gem-RT or undergoing upfront surgery. Furthermore, in all treatment groups, a more immune suppressive microenvironment was found in the tumor tissue compared to the adjacent non-tumorous tissue.© 2023. The Author(s).