PDF(Pubmed)
Abstract：
Pancreatic cancer (PC) is a clinically challenging tumor to combat due to its advanced stage at diagnosis as well as its resistance to currently available therapies. The absence of early symptoms and known detectable biomarkers renders this disease incredibly difficult to detect/manage. Recent advances in the understanding of PC biology have highlighted the importance of cancer-immune cell interactions, not only in the tumor micro-environment but also in distant systemic sites, like the bone marrow, spleen and circulating immune cells, the so-called macro-environment. The response of the macro-environment is emerging as a determining factor in tumor development by contributing to the formation of an increasingly immunogenic micro-environment promoting tumor homeostasis and progression. We will summarize the key events associated with the feedback loop between the tumor immune micro-environment (TIME) and the tumor immune macroenvironment (TIMaE) in pancreatic precancerous lesions along with how it regulates disease development and progression. In addition, liquid biopsy biomarkers capable of diagnosing PC at an early stage of onset will also be discussed. A clearer understanding of the early crosstalk between micro-environment and macro-environment could contribute to identifying new molecular therapeutic targets and biomarkers, consequently improving early PC diagnosis and treatment.
摘要：
胰腺癌（PC）是一种临床上具有挑战性的肿瘤，由于其诊断的晚期以及对当前可用疗法的抵抗力。缺乏早期症状和已知的可检测生物标志物使得这种疾病难以检测/管理。对PC生物学的理解的最新进展强调了癌症-免疫细胞相互作用的重要性。不仅在肿瘤微环境中，而且在远处的全身部位，像骨髓一样，脾脏和循环免疫细胞，所谓宏观环境。宏观环境的反应正在成为肿瘤发展的决定因素，因为它有助于形成越来越多的免疫原性微环境，从而促进肿瘤的稳态和进展。我们将总结与胰腺癌前病变中肿瘤免疫微环境（TIME）和肿瘤免疫宏观环境（TIMaE）之间的反馈循环相关的关键事件，以及它如何调节疾病的发展和进展。此外,还将讨论能够在发病早期诊断PC的液体活检生物标志物。更清楚地了解微环境和宏观环境之间的早期串扰可能有助于识别新的分子治疗靶标和生物标志物。从而改善早期PC诊断和治疗。
