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<p>Solid tumors induce systemic immune suppression, including impaired B lymphopoiesis in the bone marrow (BM). This study elucidates a novel mechanism by which remote tumors disrupt early B cell development. We demonstrate that tumor-bearing hosts exhibit skewed BM hematopoiesis favoring myeloid lineages at the expense of lymphoid lineages, specifically B cells. This impairment originates at the Common Lymphoid Progenitors (CLPs) stage. Mechanistically, monocytes, particularly CXCR2⁺ monocytes within the BM of tumor bearing mice leads to significantly elevated secretion of inflammatory cytokines TNF-α and IL-1β. These cytokines suppress CLPs differentiation into B cells. Furthermore, the enhanced secretion of TNF-α and IL-1β is mainly amplified by elevated levels of myeloid-derived S100A8/A9 proteins in the tumor-bearing BM microenvironment. Collectively, these findings identify the S100A8/A9 / TNF-α/IL-1β axis as a critical pathway disrupting B lymphopoiesis in cancer, revealing potential therapeutic targets to restore immune competence and improve immunotherapy responses.</p>

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S100A8/A9-amplified inflammation (TNF-α/IL-1β) in the bone marrow of tumor-bearing host disrupts early B cell development

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2026年3月26日

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  • Pan Yang,
  • Hao Wen,
  • Xiaoling Chen,
  • Meiling Yu,
  • Haili Yu,
  • Liang Gong,
  • Lintao Zhao,
  • Li Wang

摘要

Solid tumors induce systemic immune suppression, including impaired B lymphopoiesis in the bone marrow (BM). This study elucidates a novel mechanism by which remote tumors disrupt early B cell development. We demonstrate that tumor-bearing hosts exhibit skewed BM hematopoiesis favoring myeloid lineages at the expense of lymphoid lineages, specifically B cells. This impairment originates at the Common Lymphoid Progenitors (CLPs) stage. Mechanistically, monocytes, particularly CXCR2⁺ monocytes within the BM of tumor bearing mice leads to significantly elevated secretion of inflammatory cytokines TNF-α and IL-1β. These cytokines suppress CLPs differentiation into B cells. Furthermore, the enhanced secretion of TNF-α and IL-1β is mainly amplified by elevated levels of myeloid-derived S100A8/A9 proteins in the tumor-bearing BM microenvironment. Collectively, these findings identify the S100A8/A9 / TNF-α/IL-1β axis as a critical pathway disrupting B lymphopoiesis in cancer, revealing potential therapeutic targets to restore immune competence and improve immunotherapy responses.