One of the challenges in studying human disease is that the same condition can manifest differently across patients. However, patient variation can also be a positive thing, revealing information about the composition of diseased tissues and the relationship to disease outcome. Bill et al. used patient-to-patient variations to study how tumor microenvironments influence the progression of head and neck squamous cell carcinoma. The authors found that variations in macrophage polarity, defined by the expression of two genes, CXCL9 and SPP1, was a simple but critical feature of tumor microenvironments. The CXCL9:SPP1 ratio could characterize the abundance of antitumor immune cells in cancer, gene expression programs in each tumor-infiltrating cell type, the regulation of communication networks that dictate tumor control or progression, and the response to immunotherapy. —Priscilla N. Kelly
Tumor microenvironments (TMEs) influence cancer progression but are complex and often differ between patients. Considering that microenvironment variations may reveal rules governing intratumoral cellular programs and disease outcome, we focused on tumor-to-tumor variation to examine 52 head and neck squamous cell carcinomas. We found that macrophage polarity—defined by CXCL9 and SPP1 (CS) expression but not by conventional M1 and M2 markers—had a noticeably strong prognostic association. CS macrophage polarity also identified a highly coordinated network of either pro- or antitumor variables, which involved each tumor-associated cell type and was spatially organized. We extended these findings to other cancer indications. Overall, these results suggest that, despite their complexity, TMEs coordinate coherent responses that control human cancers and for which CS macrophage polarity is a relevant yet simple variable.
研究人类疾病面临的挑战之一是同一种病症在不同患者身上可能表现出不同的症状。然而，患者间的差异也可能成为积极因素，揭示有关病变组织构成及其与疾病结局关系的信息。Bill等人利用患者间的差异研究了肿瘤微环境如何影响头颈部鳞状细胞癌的进展。作者发现，由CXCL9和SPP1这两个基因表达所定义的巨噬细胞极性，是肿瘤微环境中一个简单但关键的特征。CXCL9:SPP1比值可以表征癌症中抗肿瘤免疫细胞的丰度、每种肿瘤浸润细胞类型的基因表达程序、决定肿瘤控制或进展的通讯网络的调控，以及对免疫疗法的反应。—Priscilla N. Kelly
肿瘤微环境（TMEs）影响癌症进展，但其结构复杂且常在患者间存在差异。考虑到微环境差异可能揭示支配瘤内细胞程序和疾病结局的规律，我们聚焦于肿瘤间的差异，对52例头颈部鳞状细胞癌进行了研究。我们发现，由CXCL9和SPP1（CS）表达而非传统M1和M2标记定义的巨噬细胞极性，具有明显强烈的预后关联。CS巨噬细胞极性也识别出一个高度协调的促肿瘤或抗肿瘤变量网络，该网络涉及每种肿瘤相关细胞类型并在空间上组织有序。我们将这些发现扩展到其他癌症适应症。总体而言，这些结果表明，尽管TMEs很复杂，但它们协调着控制人类癌症的一致性反应，而CS巨噬细胞极性是其中一个相关且简单的变量。
CXCL9:SPP1 macrophage polarity identifies a network of cellular programs that control human cancers
肿瘤(癌症)患者之家