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CD24 阻断促进口腔鳞状细胞癌中的抗肿瘤免疫。

CD24 blockade promotes anti-tumor immunity in oral squamous cell carcinoma.

机构信息

Stomatological Hospital, Southern Medical University, Guangzhou, China.

Department of Oral and Maxillofacial Surgery, Xiangya Hospital of Central South University, Changsha, China.

出版信息

Oral Dis. 2024 Mar;30(2):163-171. doi: 10.1111/odi.14367. Epub 2022 Sep 14.

Abstract

OBJECTIVES

Our study elucidates the prognostic role of cluster of differentiation (CD) 24 expression in oral squamous cell carcinoma (OSCC) and determines whether targeting CD24 enhances the anti-tumor immune response by inhibiting tumor-associated macrophages (TAMs).

MATERIALS AND METHODS

The expression of CD24 and CD68 was analyzed immunohistochemically via tissue microarrays constructed using 56 cohorts of patients with OSCC and 20 control specimens. Further, CD24 was inhibited in an allograft squamous cell carcinoma (SCC) related mouse model with CD24mAb to determine the tumor volume and weight. Changes in immune cells such as TAMs and T cells in the tumor microenvironment (TME) were analyzed by Flow cytometry. The expression of CD4, CD8, and Ki67 was analyzed via immunohistochemistry. The inhibition of CD24 was confirmed by Western blot and immunohistochemistry.

RESULTS

CD24 was overexpressed in OSCC. High expression of CD24 indicated poor survival in patients with OSCC (p = 0.0334). CD24 expression was significantly correlated with CD68 (p = 0.0424). The inhibition of CD24 delayed tumor growth in vivo. A decrease in TAMs number and an increase in T cell number were confirmed, while the ability of tumor proliferation was impaired.

CONCLUSION

Targeting CD24 could enhance anti-tumor immune response by inhibiting TAMs.

摘要

目的

本研究阐明了 CD24 表达在口腔鳞状细胞癌(OSCC)中的预后作用,并确定通过抑制肿瘤相关巨噬细胞(TAMs)是否靶向 CD24 增强抗肿瘤免疫反应。

材料与方法

通过使用 56 例 OSCC 患者和 20 例对照标本构建的组织微阵列,免疫组织化学分析 CD24 和 CD68 的表达。进一步,用 CD24mAb 抑制同种异体鳞状细胞癌(SCC)相关小鼠模型中的 CD24,以确定肿瘤体积和重量。通过流式细胞术分析肿瘤微环境(TME)中 TAMs 和 T 细胞等免疫细胞的变化。通过免疫组织化学分析 CD4、CD8 和 Ki67 的表达。通过 Western blot 和免疫组织化学验证 CD24 的抑制。

结果

CD24 在 OSCC 中过表达。CD24 的高表达表明 OSCC 患者的生存不良(p=0.0334)。CD24 表达与 CD68 显著相关(p=0.0424)。CD24 的抑制可延迟体内肿瘤生长。证实 TAMs 数量减少和 T 细胞数量增加,同时肿瘤增殖能力受损。

结论

靶向 CD24 可能通过抑制 TAMs 增强抗肿瘤免疫反应。

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