Department of Surgery, Amsterdam UMC, Vrije Universiteit Amsterdam, Amsterdam, The Netherlands.
Cancer Center Amsterdam, Amsterdam, The Netherlands.
J Cancer Res Clin Oncol. 2023 Nov;149(16):14731-14743. doi: 10.1007/s00432-023-05219-7. Epub 2023 Aug 17.
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.
越来越多可切除和边界可切除的胰腺导管腺癌患者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在很大程度上尚不清楚。我们分析了接受新辅助治疗的患者与接受直接手术的患者的胰腺肿瘤组织样本中的免疫微环境，以了解治疗后免疫环境的变化。
对接受直接手术（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多光谱成像。由专门的胰腺病理学家从肿瘤的中央部分和侵袭前缘（通过切除的静脉或静脉表面）选择样本，并随后使用 Vectra Polaris 进行分析。
与接受新辅助 gem-RT/gem-RT 或直接手术的患者相比，接受新辅助 FOLFIRINOX 治疗的患者肿瘤组织中表现出更具炎症性的免疫特征，T 调节细胞较少，CD8 T 细胞较多。此外，CD163 巨噬细胞减少，并且在接受新辅助 FOLFIRINOX 的患者中发现 CD163 巨噬细胞与 CD163 巨噬细胞的比值更高。在所有治疗组中，肿瘤组织中 FoxP3 B 细胞的百分比明显高于相邻组织。此外，直接手术或接受新辅助 gem-RT 的患者的肿瘤组织中 T 调节细胞增加。在 gem-RT 组中，肿瘤组织中 CD8 T 细胞减少，CD163 巨噬细胞与 CD8 比值升高，提示肿瘤组织中存在更具免疫抑制性的特征。
与接受新辅助 gem-RT 或直接手术的患者相比，接受新辅助 FOLFIRINOX 的患者表现出更具炎症性的免疫特征。此外，在所有治疗组中，与相邻非肿瘤组织相比，肿瘤组织中存在更具免疫抑制性的微环境。
