Aging is a risk factor for cancer but the mechanisms by which aging affects tumor control remain unclear. In Science, Park et al. find that aging is associated with enhanced emergency myelopoiesis, resulting in the accumulation of IL-1α-producing myeloid progenitor (MP)-like cells in tumors that drive tumor growth. Using a model of non-small-cell lung cancer (NSCLC), the authors find that old mice exhibited a greater tumor burden than young mice, with an increased accumulation of monocyte-derived macrophages and lung MPs in the tumor. When older mice underwent a bone marrow transplant from younger mice the tumor burden was decreased, and reciprocally when young mice received a bone marrow transplant from older mice the tumor burden was increased. IL-1α was upregulated in MPs from tumors from older mice and blocking IL-1α delayed tumor progression, reduced MPs in the tumor and reduced commitment of hematopoietic stem cells (HSC) to the granulocyte–monocyte progenitor lineage in the bone marrow. HSCs from healthy older mice downregulated expression of Dnmt3a, and the treatment of monocytes with a DNMT3A inhibitor resulted in increased IL-1α production. When older tumor-bearing mice were treated with PD-1 blocking antibody and the IL-1R1 antagonist anakinra, the clearance of tumor cell was enhanced compared with PD-1 blockade alone, with an increased NK cell response. The authors suggest that IL-1R inhibitors could be used in the treatment of NSCLC in older patients.

Original reference: Science https://doi.org/10.1126/science.adn0327 (2024)

衰老是癌症的一个危险因素，但衰老影响肿瘤控制的机制仍不清楚。在《科学》杂志上，Park 等人发现衰老与紧急骨髓生成增强有关，导致产生 IL-1α 的髓样祖细胞 （MP） 样细胞在驱动肿瘤生长的肿瘤中积累。使用非小细胞肺癌 （NSCLC） 模型，作者发现老年小鼠比年轻小鼠表现出更大的肿瘤负荷，单核细胞衍生的巨噬细胞和肺 MP 在肿瘤中的积累增加。当老年小鼠接受年轻小鼠的骨髓移植时，肿瘤负荷降低，反之，当年轻小鼠接受老年小鼠的骨髓移植时，肿瘤负荷增加。IL-1α 在老年小鼠肿瘤的 MPs 中上调，阻断 IL-1α 延缓肿瘤进展，减少肿瘤中的 MP，并减少造血干细胞 （HSC） 对骨髓中粒细胞-单核细胞祖细胞谱系的定型。来自健康老年小鼠的 HSC 下调 Dnmt3a 的表达，用 DNMT3A 抑制剂处理单核细胞导致 IL-1α 产生增加。当用 PD-1 阻断抗体和 IL-1R1 拮抗剂阿那白滞素处理老年荷瘤小鼠时，与单独使用 PD-1 阻断剂相比，肿瘤细胞的清除能力增强，NK 细胞反应增加。作者建议 IL-1R 抑制剂可用于老年患者的 NSCLC 治疗。

Original reference: Science https://doi.org/10.1126/science.adn0327 (2024)