Obesity is a disease characterized by chronic low-grade systemic inflammation and has been causally linked to the development of 13 cancer types. Several studies have been undertaken to determine if tumors evolving in obese environments adapt differential interactions with immune cells and if this can be connected to disease outcome. Most of these studies have been limited to single cell lines and tumor models and analysis of limited immune cell populations. Given the multicellular complexity of the immune system and its dysregulation in obesity, we applied high-dimensional suspension mass cytometry to investigate how obesity affects tumor immunity. We used a 36-marker immune-focused mass cytometry panel to interrogate the immune landscape of orthotopic syngeneic mouse models of pancreatic and breast cancer. Unanchored batch correction was implemented to enable simultaneous analysis of tumor cohorts to uncover the immunotypes of each cancer model and reveal remarkably model-specific immune regulation. In the E0771 breast cancer model, we demonstrate an important link to obesity with an increase in two T cell suppressive cell types and a decrease in CD8 T-cells.

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肥胖肿瘤微环境的高维免疫分型显示模型特异性适应性

肥胖是一种以慢性低度全身性炎症为特征的疾病，与13种癌症的发展有因果关系。已经进行了数项研究来确定在肥胖环境中发展的肿瘤是否适应与免疫细胞的差异相互作用，以及这是否可以与疾病结果相关。这些研究大多限于单细胞系和肿瘤模型以及有限免疫细胞群的分析。考虑到免疫系统的多细胞复杂性及其在肥胖症中的失调，我们应用了高维悬浮细胞计数技术来研究肥胖症如何影响肿瘤免疫力。我们使用了一个36标记的以免疫为重点的大规模流式细胞仪小组来研究胰腺癌和乳腺癌的原位同基因小鼠模型的免疫状况。实施了无固定批次校正功能，以便能够同时分析肿瘤队列，从而发现每种癌症模型的免疫类型，并显着揭示模型特异性的免疫调节。在E0771乳腺癌模型中，我们证明了与肥胖的重要联系，其中包括两种T细胞抑制细胞类型的增加和CD8 T细胞的减少。