Chemokine-mucinome interplay in shaping the heterogeneous tumor microenvironment of pancreatic cancer.
Chemokine-mucinome interplay in shaping the heterogeneous tumor microenvironment of pancreatic cancer.
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DOI：
10.1016/j.semcancer.2022.03.022
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发表时间：
2022-11
影响因子：
14.5
通讯作者：
Batra, Surinder K.
中科院分区：
文献类型：
--
作者：
Ganguly, Koelina;Shah, Ashu;Atri, Pranita;Rauth, Sanchita;Ponnusamy, Moorthy P.;Kumar, Sushil;Batra, Surinder K.
胰腺癌（PC）以复杂的免疫抑制、纤维化肿瘤微环境（TME）、致癌分子改变和粘蛋白异常表达为例。癌细胞、癌症相关成纤维细胞（CAFs）和由可溶性因子和炎症介质（包括细胞因子、趋化因子、活性氧（ROS））介导的免疫细胞之间的持续串音促进肿瘤细胞及其微环境中向免疫逃逸表型的动态时间转换，从而促进疾病进展。趋化因子已经在PC发病机制中得到了研究，尽管在粘蛋白、肿瘤糖萼和TME异质性（CAFs和免疫细胞）的背景下研究较少。通过对PC患者转录组数据的相关分析，现有文献的支持，以及基于科学论证的疾病发病机制的推测外推，我们在这篇综述中总结了对PC中基质调节和免疫抑制过程中趋化因子-黏液素组相互作用的全面理解。未来的研究应该集中在解读趋化因子介导的糖萼成熟、免疫浸润和ca相关免疫抑制的复杂性。从这些研究中提取的知识将有助于将血清中黏液趋化因子丰度与患者胰腺肿瘤的机制关联起来，这可能有助于预测和分层PC患者进行免疫治疗。
Pancreatic cancer (PC) is exemplified by a complex immune-suppressive, fibrotic tumor microenvironment (TME), oncogenic molecular alterations, and aberrant expression of mucins. The constant crosstalk between cancer cells, cancer-associated fibroblasts (CAFs), and the immune cells mediated by the soluble factors and inflammatory mediators including cytokines, chemokines, reactive oxygen species (ROS) promote the dynamic temporal switch towards an immune-escape phenotype in the neoplastic cells and its microenvironment that bolsters disease progression. Chemokines have been studied in PC pathogenesis, albeit poorly in the context of mucins, tumor glycocalyx, and TME heterogeneity (CAFs and immune cells). With correlative analysis from PC patients’ transcriptome data, support from available literature, and scientific arguments-based speculative extrapolations in terms of disease pathogenesis, we have summarized in this review a comprehensive understanding of chemokine-mucinome interplay during stromal modulation and immune-suppression in PC. Future studies should focus on deciphering the complexities of chemokine-mediated control of glycocalyx maturation, immune infiltration, and CAF-associated immune suppression. Knowledge extracted from such studies will be beneficial to mechanistically correlate the mucin-chemokine abundance in serum versus pancreatic tumors of patients, which may aid in prognostication and stratification of PC patients for immunotherapy.
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