Primary tumors from mucosal barrier organs drive unique eosinophil infiltration patterns and clinical associations.
Primary tumors from mucosal barrier organs drive unique eosinophil infiltration patterns and clinical associations.
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DOI：
10.1080/2162402x.2020.1859732
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发表时间：
2020-12-30
期刊：
影响因子：
7.2
通讯作者：
Munitz A
中科院分区：
文献类型：
--
作者：
Grisaru-Tal S;Itan M;Grass DG;Torres-Roca J;Eschrich SA;Gordon Y;Dolitzky A;Hazut I;Avlas S;Jacobsen EA;Ziv-Baran T;Munitz A
嗜酸性粒细胞是骨髓来源的粒细胞，在过敏性疾病中发挥关键的效应作用。尽管如此，最近的数据强调了嗜酸性粒细胞在肿瘤微环境（TME）中的重要作用。嗜酸性粒细胞被认为具有多效性和可能相互冲突的功能，这可能至少部分归因于TME中嗜酸性粒细胞数量的变化。因此，需要一种可靠、定量和稳健的方法来评估TME中的嗜酸性粒细胞浸润。这种类型的方法可以使这些细胞的鉴定标准化，并促进下一代假设驱动的机制研究。为此，我们采用标准化方法对不同解剖部位的多发原发肿瘤进行了综合分析。对10469例原发性肿瘤基因组图谱的生物信息学分析显示，不同肿瘤内嗜酸性粒细胞丰度可分为高、中、低嗜酸性粒细胞水平三组。因此，在代表所有三种类型（结肠和食道-高；肺-中；宫颈、卵巢和乳房-低）的六个肿瘤的组织肿瘤阵列中，确定了嗜酸性粒细胞的丰度和空间分布。除乳腺癌外，嗜酸性粒细胞主要局限于肿瘤间质。重要的是，肿瘤解剖部位被确定为嗜酸性粒细胞间质密度的主要预测因素，突出了粘膜屏障器官与非粘膜屏障器官之间的区别。这些发现增强了我们对TME中嗜酸性粒细胞多样性的理解，并为未来评估这些细胞活性的实验提供了令人信服的理论依据。
Eosinophils are bone marrow-derived granulocytes that display key effector functions in allergic diseases. Nonetheless, recent data highlight important roles for eosinophils in the tumor microenvironment (TME). Eosinophils have been attributed with pleiotropic and perhaps conflicting functions, which may be attributed at least in part to variations in eosinophil quantitation in the TME. Thus, a reliable, quantitative, and robust method for the assessment of eosinophilic infiltration in the TME is required. This type of methodology could standardize the identification of these cells and promote the subsequent generation of hypothesis-driven mechanistic studies. To this end, we conducted a comprehensive analysis of multiple primary tumors from distinct anatomical sites using a standardized method. Bioinformatics analysis of 10,469 genomically profiled primary tumors revealed that eosinophil abundance within different tumors can be categorized into three groups representing tumors with high, intermediate, and low eosinophil levels. Consequently, eosinophil abundance, as well as spatial distribution, was determined in tissue tumor arrays of six tumors representing all three classifications (colon and esophagus – high; lung – intermediate; cervix, ovary, and breast – low). With the exception of breast cancer, eosinophils were mainly localized in the tumor stroma. Importantly, the tumor anatomical site was identified as the primary predictive factor of eosinophil stromal density highlighting a distinction between mucosal-barrier organs versus non-mucosal barrier organs. These findings enhance our understanding of eosinophil diversity in the TME and provide a compelling rationale for future experiments assessing the activity of these cells.