美国印第安纳大学医学院Ashiq Masood研究组，通过对原发性和转移性胰腺癌的空间转录组分析发现，肿瘤微环境具有异质性。相关论文于2024年9月18日发表在《自然—遗传学》杂志上。

通过利用空间分辨转录组学，对匹配的原发性和转移性胰腺导管腺癌（PDAC）样本进行分析，研究人员发现了跨解剖区域的纤维化、代谢和免疫抑制空间生态学的连续性。该研究观察到的空间肿瘤微环境异质性，超出了之前在PDAC中的发现。

通过比较分析，研究发现空间生态学在原发部位和转移部位之间表现出明显的富集，这意味着肿瘤生存和发展会适应局部环境。

侵袭性肿瘤的边界生态学同时表现出，促肿瘤生成和抗肿瘤生成细胞类型的富集，表明这是一个潜在的免疫治疗靶点。不同患者肿瘤生态学异质性证明，绘制患者特异性转录图以制定个性化治疗策略的必要性。

总之，该研究结果提供了对转移性PDAC生物学的重要见解，为未来的治疗和分子研究提供了宝贵的资源。

研究人员表示，尽管已经获得了切除胰腺导管腺癌的空间、细胞和分子图谱，但其转移生态学的特征仍然未知。

附：英文原文

Title: Spatial transcriptomic analysis of primary and metastatic pancreatic cancers highlights tumor microenvironmental heterogeneity

Author: Khaliq, Ateeq M., Rajamohan, Meenakshi, Saeed, Omer, Mansouri, Kimia, Adil, Asif, Zhang, Chi, Turk, Anita, Carstens, Julienne L., House, Michael, Hayat, Sikander, Nagaraju, Ganji P., Pappas, Sam G., Wang, Y. Alan., Zyromski, Nicholas J., Opyrchal, Mateusz, Lee, Kelvin P., OHagan, Heather, El Rayes, Bassel, Masood, Ashiq

Issue&Volume: 2024-09-18

Abstract: Although the spatial, cellular and molecular landscapes of resected pancreatic ductal adenocarcinoma (PDAC) are well documented, the characteristics of its metastatic ecology remain elusive. By applying spatially resolved transcriptomics to matched primary and metastatic PDAC samples, we discovered a conserved continuum of fibrotic, metabolic and immunosuppressive spatial ecotypes across anatomical regions. We observed spatial tumor microenvironment heterogeneity spanning beyond that previously appreciated in PDAC. Through comparative analysis, we show that the spatial ecotypes exhibit distinct enrichment between primary and metastatic sites, implying adaptability to the local environment for survival and progression. The invasive border ecotype exhibits both pro-tumorigenic and anti-tumorigenic cell-type enrichment, suggesting a potential immunotherapy target. The ecotype heterogeneity across patients emphasizes the need to map individual patient landscapes to develop personalized treatment strategies. Collectively, our findings provide critical insights into metastatic PDAC biology and serve as a valuable resource for future therapeutic exploration and molecular investigations.

DOI: 10.1038/s41588-024-01914-4

Source: https://www.nature.com/articles/s41588-024-01914-4