跨脏器的免疫协调对于癌症的发展和进展至关重要。 众所周知，肿瘤中的敌意代谢微环境是有效抗癌免疫的主要障碍。 然而，超越肿瘤的继发淋巴器官内的代谢变化是否会影响抗癌免疫仍然不明确。 通过正电子发射计算机断层扫描，我们表明人类和小鼠患乳腺癌的脾脏被代谢重编程为糖酵解状态。 这种脾脏中葡萄糖消耗的增加主要发生在经胚外造血和骨髓招募产生的嗜中性粒细胞中。 白髓中的这些嗜中性粒细胞创建了一个缺乏葡萄糖的微环境，进而通过损害丙酮酸激酶M2及其对STAT5的作用而诱导T细胞的耐受性，从而损害其抗肿瘤活性。 此外，脾脏基质细胞产生的CCL9趋化因子对脾脏嗜中性粒细胞的积累起着核心作用，而CCR1受体的阻断有利于肿瘤的扑灭。 因此，嗜中性粒细胞在代谢上影响脾脏微环境并控制抗肿瘤T细胞反应。© 2023. 作者，由Springer Nature Limited独家许可。

The coordination of immunity across organs is fundamental to cancer development and progression. It is well known that the hostile metabolic microenvironment in the tumour is a major obstacle to effective anti-tumour immunity. However, whether metabolic alterations in secondary lymphoid tissues beyond the tumour can affect anti-tumour immunity remains elusive. Using positron-emission tomography-computed tomography, we show that the spleens of humans and mice with breast cancer are metabolically reprogrammed to a glycolytic state. Such an increase in glucose consumption in the spleen primarily occurs in neutrophils generated by extramedullary haematopoiesis and recruitment from the bone marrow. These neutrophils in the white pulp create a glucose-deprived microenvironment, which, in turn, induces T cell anergy by impairing pyruvate kinase M2 and its action on STAT5, thus compromising their anti-tumour activities. Furthermore, CCL9 chemokine produced by splenic stromal cells is central to splenic neutrophil accumulation, and blockade of the CCR1 receptor favours tumour eradication. Thus, neutrophils metabolically influence the spleen microenvironment and control anti-tumour T cell responses.© 2023. The Author(s), under exclusive licence to Springer Nature Limited.