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)