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脾切除术对小鼠结肠癌模型中原发性肿瘤与转移性肿瘤的生长具有相反的影响。

Splenectomy has opposite effects on the growth of primary compared with metastatic tumors in a murine colon cancer model.

机构信息

Department of Surgery, Jichi Medical University, Yakushiji 3311-1, Shimotsuke, Tochigi, 329-0498, Japan.

Department of Clinical Oncology, Jichi Medical University Hospital, Shimotsuke, Japan.

出版信息

Sci Rep. 2024 Feb 24;14(1):4496. doi: 10.1038/s41598-024-54768-5.

Abstract

The spleen is a key source of circulating and tumor-infiltrating immune cells. However, the effect of splenectomy on tumor growth remains unclear. At 3 weeks after splenectomy, we subcutaneously injected LuM1 cells into BALB/c mice and evaluated the growth of primary tumors and lung metastases at 4 weeks after tumor inoculation. In addition, we examined the phenotypes of immune cells in peripheral blood by using flow cytometry and in tumor tissue by using multiplex immunohistochemistry. The growth of primary tumors was reduced in splenectomized mice compared with the sham-operated group. Conversely, splenectomized mice had more lung metastases. Splenectomized mice had fewer CD11bcells, especially monocytic MDSCs (CD11bGr-1Ly6c), and NK cells (CD49bCD335). The proportion of NK cells was inversely correlated with the number of lung metastases. In splenectomized mice, the density of CD3 and granzyme B CD8 T cells was increased, with fewer M2-type macrophages in primary tumors, but NK cells were decreased markedly in lung. Splenectomy concurrently enhances T cell-mediated acquired immunity by reducing the number of monocytic MDSCs and suppresses innate immunity by decreasing the number of NK cells. Splenectomy has opposite effects on primary and metastatic lesions through differential regulation on these two immune systems.

摘要

脾脏是循环和肿瘤浸润免疫细胞的主要来源。然而,脾切除术对肿瘤生长的影响仍不清楚。在脾切除后 3 周,我们将 LuM1 细胞皮下注射到 BALB/c 小鼠中,并在肿瘤接种后 4 周评估原发肿瘤和肺转移的生长情况。此外,我们通过流式细胞术检测外周血免疫细胞的表型,通过多重免疫组化检测肿瘤组织中的免疫细胞表型。与假手术组相比,脾切除组的原发肿瘤生长减少。相反,脾切除组有更多的肺转移。脾切除组的 CD11b 细胞(尤其是单核细胞来源的髓系抑制细胞(CD11bGr-1Ly6c)和 NK 细胞(CD49bCD335)较少。NK 细胞的比例与肺转移的数量呈负相关。在脾切除组中,CD3 和颗粒酶 B CD8 T 细胞的密度增加,原发性肿瘤中 M2 型巨噬细胞减少,但 NK 细胞在肺中明显减少。脾切除术通过减少单核细胞来源的髓系抑制细胞的数量增强 T 细胞介导的获得性免疫,通过减少 NK 细胞的数量抑制固有免疫。脾切除术通过对这两种免疫系统的不同调节对原发和转移病变产生相反的影响。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3cb8/10894273/1cfff38bfae4/41598_2024_54768_Fig1_HTML.jpg

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