美国康奈尔大学J. Magarian Blander团队近期取得重要工作进展，他们研究提出，基质炎性小体Ras能预防Myc驱动的淋巴瘤发生。相关研究成果2025年1月2日在线发表于《自然—免疫学》杂志上。

据介绍，炎症小体在癌症中起着多方面的作用，但对其在癌前细胞转化过程中的功能知之甚少。

研究人员报道了炎性小体通过Ras抑制抑制恶性转化的稳态功能。研究人员发现炎症小体缺陷小鼠骨髓中造血干细胞（HSC）增殖增加。炎症因子缺乏间质内的HSC表达Ras信号，该信号与Ras通路和癌症相关转录物的增加以及细胞因子、趋化因子和生长因子受体水平的升高有关。

基质炎性小体缺乏在HSC内建立了一种稳定的Ras依赖性有丝分裂状态，这在B细胞淋巴瘤自发模型中Myc失调时促进了后代B细胞淋巴瘤的发生，并缩短了其癌前阶段，导致恶性肿瘤发病更快。因此，间质炎性体通过抑制Ras来破坏最常见的致癌Myc-Ras合作，并建立一种天然的防御机制来防止向恶性肿瘤的转变，从而保持组织平衡。

总之，这一研究能为血液系统恶性肿瘤的预防性治疗提供信息。

附：英文原文

Title: A stromal inflammasome Ras safeguard against Myc-driven lymphomagenesis

Author: Kent, Andrew, Yee Mon, Kristel Joy, Hutchins, Zachary, Putzel, Gregory, Zhigarev, Dmitry, Grier, Alexander, Jia, Baosen, Kortlever, Roderik M., Barbet, Gaetan, Evan, Gerard I., Blander, J. Magarian

Issue&Volume: 2025-01-02

Abstract: The inflammasome plays multifaceted roles in cancer, but less is known about its function during premalignancy upon initial cell transformation. We report a homeostatic function of the inflammasome in suppressing malignant transformation through Ras inhibition. We identified increased hematopoietic stem cell (HSC) proliferation within the bone marrow of inflammasome-deficient mice. HSCs within an inflammasome-deficient stroma expressed a Ras signature associated with increased Ras pathway- and cancer-related transcripts and heightened levels of cytokine, chemokine and growth factor receptors. Stromal inflammasome deficiency established a poised Ras-dependent mitogenic state within HSCs, which fueled progeny B cell lymphomagenesis upon Myc deregulation in a spontaneous model of B cell lymphoma, and shortened its premalignant stage leading to faster onset of malignancy. Thus, the stromal inflammasome preserves tissue balance by restraining Ras to disrupt the most common oncogenic Myc–Ras cooperation and establish a natural defense against transition to malignancy. These findings should inform preventative therapies against hematological malignancies.

DOI: 10.1038/s41590-024-02028-z

Source: https://www.nature.com/articles/s41590-024-02028-z