Hematopoietic-derived cells are integral components of the tumor microenvironment and serve as critical mediators of tumor-host interactions. Host cells derived from myeloid and lymphoid lineages perform well-established functions linked to cancer development, progression and response to therapy. It is unclear whether host erythroid cells also contribute to shaping the path that cancer can take, but emerging evidence points to this possibility. Here we show that tumor-promoting environmental stress and tumor-induced hemodynamic changes trigger renal erythropoietin production and erythropoietin-dependent expansion of splenic erythroid cell populations in mice. These erythroid cells display molecular features indicative of an immature erythroid phenotype, such as the expression of both CD71 and TER119 and the retention of intact nuclei, and express genes encoding immune checkpoint molecules. Nucleated erythroid cells with similar properties are present in mouse and human tumor tissues. Antibody-mediated erythropoietin blockade reduces tumor-responsive erythroid cell induction and tumor growth. These findings reveal the potential of tumor-induced erythropoietin and erythroid cells as targets for cancer treatment. Implications: Our study identifies erythropoietin and erythroid cells as novel players in tumor-host interactions and highlights the involvement of multi-organ signaling events in their induction in response to environmental stress and tumor growth.

中文翻译：

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多器官信号动员肿瘤相关红细胞表达免疫检查点分子

造血细胞是肿瘤微环境的组成部分，是肿瘤-宿主相互作用的关键介质。源自骨髓和淋巴谱系的宿主细胞具有与癌症发展、进展和对治疗的反应相关的公认功能。目前尚不清楚宿主红细胞是否也有助于塑造癌症的路径，但新出现的证据表明了这种可能性。在这里，我们展示了促进肿瘤的环境压力和肿瘤诱导的血流动力学变化触发了小鼠肾脏促红细胞生成素的产生和脾红细胞群的促红细胞生成素依赖性扩增。这些红系细胞显示出指示未成熟红系表型的分子特征，例如 CD71 和 TER119 的表达以及完整细胞核的保留，并表达编码免疫检查点分子的基因。具有相似特性的有核红细胞存在于小鼠和人类肿瘤组织中。抗体介导的促红细胞生成素阻断降低了肿瘤反应性红细胞诱导和肿瘤生长。这些发现揭示了肿瘤诱导的促红细胞生成素和类红细胞作为癌症治疗靶点的潜力。启示：我们的研究将促红细胞生成素和类红细胞确定为肿瘤-宿主相互作用中的新参与者，并强调了多器官信号事件在它们对环境压力和肿瘤生长的反应中的诱导作用。抗体介导的促红细胞生成素阻断降低了肿瘤反应性红细胞诱导和肿瘤生长。这些发现揭示了肿瘤诱导的促红细胞生成素和类红细胞作为癌症治疗靶点的潜力。启示：我们的研究将促红细胞生成素和类红细胞确定为肿瘤-宿主相互作用中的新参与者，并强调了多器官信号事件在它们对环境压力和肿瘤生长的反应中的诱导作用。抗体介导的促红细胞生成素阻断降低了肿瘤反应性红细胞诱导和肿瘤生长。这些发现揭示了肿瘤诱导的促红细胞生成素和类红细胞作为癌症治疗靶点的潜力。启示：我们的研究将促红细胞生成素和类红细胞确定为肿瘤-宿主相互作用中的新参与者，并强调了多器官信号事件在它们对环境压力和肿瘤生长的反应中的诱导作用。