The tumor immune microenvironment in long-term survival resected pancreatic cancer patients. The tumor immune microenvironment in long-term survival resected pancreatic cancer patients

This study aimed to elucidate immunological and microbial factors contributing to prolonged survival in pancreatic ductal adenocarcinoma (PDAC) patients, providing valuable guidance for treatment strategies that enhance efficacy. To accomplish this, we performed metatranscriptomics analyses and IF staining analyses to map the TIME in PDAC tumors from treatment-naïve short-term survivors (a cancer-specific survival of shorter than six months, STS) and long-term survivors (a cancer-specific survival over five years, LTS). In conclusion, our study unveiled a distinctive, yet intricate tumore immune microenvironment associated with prolonged survival in PDAC. This profile includes a decrease in pro-tumoral M2 and M0 macrophages, along with an increase in plasma B cells, all linked to a better prognosis in PDAC. Future research should be directed towards a more comprehensive understanding of the role of B cells in pancreatic cancer and the modulation of M2 macrophage polarization. Such insights will be invaluable in tailoring personalized therapeutic strategies to enhance patient outcomes. Overall design: To understand the prerequisites for long-term survival following surgical resection in PDAC patients, we performed the metatranscriptomic analyses and multiplex immunofluorescence, between STS and LTS. Surgical specimens were formalin-fixed paraffin-embedded (FFPE) and stored. Patients were treatment-naive prior to surgery.

本研究旨在阐明影响胰腺导管腺癌（pancreatic ductal adenocarcinoma, PDAC）患者长期存活的免疫与微生物相关因素，为优化治疗策略、提升临床疗效提供重要参考依据。
为达成此研究目标，我们开展了宏转录组学（metatranscriptomics）分析与免疫荧光（immunofluorescence, IF）染色分析，以绘制未经治疗的短期存活者（癌症特异性生存期短于6个月，简称STS）与长期存活者（癌症特异性生存期超过5年，简称LTS）的胰腺导管腺癌肿瘤免疫微环境（tumor immune microenvironment, TIME）图谱。
综上，本研究揭示了与胰腺导管腺癌患者长期存活相关的独特且复杂的肿瘤免疫微环境特征：促肿瘤型M2及M0巨噬细胞浸润减少，同时浆细胞B细胞（plasma B cells）浸润增加，上述变化均与胰腺导管腺癌更佳的预后密切相关。
未来的研究应进一步全面解析B细胞在胰腺癌中的作用，以及M2巨噬细胞极化的调控机制。此类研究成果将为定制个性化治疗策略以改善患者预后提供极为宝贵的参考价值。
实验整体设计：为阐明胰腺导管腺癌患者术后长期存活的前置条件，我们针对STS与LTS两组患者开展了宏转录组学分析与多重免疫荧光分析。所有手术标本均经福尔马林固定石蜡包埋（formalin-fixed paraffin-embedded, FFPE）并妥善保存，且所有患者术前均未接受过任何治疗。