Immune cells in the tumor microenvironment have prognostic value. In preclinical models, recruitment and infiltration of these cells depends on immune cell homing (ICH) genes such as chemokines, cell adhesion molecules, and integrins. We hypothesized ICH ligands CXCL9-11 and CCL2-5 would be associated with intratumoral T-cells, while CXCL13 would be more associated with B-cell infiltrates. Samples of human melanoma were submitted for gene expression analysis and immune cells identified by immunohistochemistry. Associations between the two were evaluated with unsupervised hierarchical clustering using correlation matrices from Spearman rank tests. Univariate analysis performed Mann–Whitney tests. For 119 melanoma specimens, analysis of 78 ICH genes revealed association among genes with nonspecific increase of multiple immune cell subsets: CD45+, CD8+ and CD4+ T-cells, CD20+ B-cells, CD138+ plasma cells, and CD56+ NK-cells. ICH genes most associated with these infiltrates included ITGB2, ITGAL, CCL19, CXCL13, plus receptor/ligand pairs CXCL9 and CXCL10 with CXCR3; CCL4 and CCL5 with CCR5. This top ICH gene expression signature was also associated with genes representing immune-activation and effector function. In contrast, CD163+ M2-macrophages was weakly associated with a different ICH gene signature. These data do not support our hypothesis that each immune cell subset is uniquely associated with specific ICH genes. Instead, a larger set of ICH genes identifies melanomas with concordant infiltration of B-cell and T-cell lineages, while CD163+ M2-macrophage infiltration suggesting alternate mechanisms for their recruitment. Future studies should explore the extent ICH gene signature contributes to tertiary lymphoid structures or cross-talk between homing pathways.

中文翻译：

---

免疫细胞归巢基因特征与人黑色素瘤淋巴细胞亚群浸润的关联：与 CD163+ 骨髓细胞浸润的不一致

肿瘤微环境中的免疫细胞具有预后价值。在临床前模型中，这些细胞的募集和浸润取决于免疫细胞归巢 (ICH) 基因，例如趋化因子、细胞粘附分子和整合素。我们假设 ICH 配体 CXCL9-11 和 CCL2-5 与肿瘤内 T 细胞相关，而 CXCL13 与 B 细胞浸润更相关。提交人类黑色素瘤样本进行基因表达分析，并通过免疫组织化学鉴定免疫细胞。使用 Spearman 秩检验的相关矩阵通过无监督层次聚类评估两者之间的关联。单变量分析执行 Mann-Whitney 检验。对于 119 个黑色素瘤标本，对 78 个 ICH 基因的分析揭示了基因与多个免疫细胞亚群的非特异性增加之间的关联：CD45+、CD8+ 和 CD4+ T 细胞、CD20+ B 细胞、CD138+ 浆细胞和 CD56+ NK 细胞。与这些浸润最相关的 ICH 基因包括 ITGB2、ITGAL、CCL19、CXCL13，以及具有 CXCR3 的受体/配体对 CXCL9 和 CXCL10；CCL4 和 CCL5 与 CCR5。这种顶级 ICH 基因表达特征也与代表免疫激活和效应功能的基因相关。相比之下，CD163+ M2-巨噬细胞与不同的 ICH 基因特征弱相关。这些数据不支持我们的假设，即每个免疫细胞亚群都与特定的 ICH 基因唯一相关。相反，一组更大的 ICH 基因识别出具有 B 细胞和 T 细胞谱系一致浸润的黑色素瘤，而 CD163+ M2 巨噬细胞浸润表明了它们募集的替代机制。