Department of Internal Medicine, Radboud University Medical Center, Nijmegen, The Netherlands.
Radiotherapy and OncoImmunology Laboratory, Department of Radiation Oncology, Radboud University Medical Center, Nijmegen, The Netherlands.
Nat Commun. 2022 Oct 18;13(1):6149. doi: 10.1038/s41467-022-33907-4.
Myeloid cells, crucial players in antitumoral defense, are affected by tumor-derived factors and treatment. The role of myeloid cells and their progenitors prior to tumor infiltration is poorly understood. Here we show single-cell transcriptomics and functional analyses of the myeloid cell lineage in patients with non-medullary thyroid carcinoma (TC) and multinodular goiter, before and after treatment with radioactive iodine compared to healthy controls. Integrative data analysis indicates that monocytes of TC patients have transcriptional upregulation of antigen presentation, reduced cytokine production capacity, and overproduction of reactive oxygen species. Interestingly, these cancer-related pathological changes are partially removed upon treatment. In bone marrow, TC patients tend to shift from myelopoiesis towards lymphopoiesis, reflected in transcriptional differences. Taken together, distinct transcriptional and functional changes in myeloid cells arise before their infiltration of the tumor and are already initiated in bone marrow, which suggests an active role in forming the tumor immune microenvironment.
髓系细胞是抗肿瘤防御的关键参与者，它们受到肿瘤衍生因子和治疗的影响。在肿瘤浸润之前，髓系细胞及其前体细胞的作用还知之甚少。在这里，我们展示了非髓样甲状腺癌 (TC) 和多结节性甲状腺肿患者的髓系细胞谱系的单细胞转录组学和功能分析，这些患者在接受放射性碘治疗前后与健康对照组进行了比较。综合数据分析表明，TC 患者的单核细胞在抗原呈递方面存在转录上调，细胞因子产生能力降低，活性氧过度产生。有趣的是，这些与癌症相关的病理变化在治疗后部分消除。在骨髓中，TC 患者倾向于从骨髓生成向淋巴生成转移，这反映在转录差异上。总之，在髓系细胞浸润肿瘤之前，就会出现明显的转录和功能变化，并且已经在骨髓中开始，这表明它们在形成肿瘤免疫微环境中发挥着积极作用。
