PRMT5 highly expressed on CD16 + CD56- natural killer cells is correlated with NK cells exhaustion in colorectal cancer mesenchyme.

IF 5.1 2区 医学 Q2 IMMUNOLOGY
Zunzhen Nie, Juanjuan Chang, Zhiqin Yang, Kaixuan Zeng, Yuangang Liu, Qian Tu, Chao Wang, Qingguo Yan, Hai Shi, Ying Guo
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Abstract

Objective: To investigate the relationships between changes in the phenotype of natural killer cells (NK cells) in the microenvironment of colorectal cancer (CRC) and the expression of important immune checkpoints. To assess the expression level of CD16 bright CD56 negative (CD16 + CD56-) NK cell-associated immune checkpoints, including protein arginine methyltransferase 5 (PRMT5) and T-cell immunoreceptor with Ig and ITIM domains (TIGIT), single-immunoglobulin interleukin-1-related receptor (SIGIRR), in CRC mesenchyme.

Methods: A total of 194 patients who were diagnosed with CRC were screened. The percentage of NK cells and the expression levels of their surface receptors, including PRMT5, CD56, CD69, TIGIT, CD16, IFN-γ, and SIGIRR, in the tumor microenvironment (TME) of CRC were assessed. Immunohistochemical staining, multiplex immunohistochemistry, and single-cell sequencing were performed.

Results: Compared with normal mesenchyme, NK cells were less in CRC mesenchyme. The percentage of CD16 + CD56- NK cells in tumor mesenchyme was significantly higher, the number of CD16 + NK cells was more, and the number of CD56 + NK cells was less in CRC mesenchyme. High expression of TIGIT and PRMT5 expression affected the progression of CRC. The expression of PRMT5 and SIGIRR expression was significantly increased in CD16 + CD56- NK cells, and both genes were identified as important morbidity factors. PRMT5 and SIGIRR may contribute to the phenotype changes of NK cells in CRC.

Conclusion: The microenvironment of CRC is in an immunosuppressive state characterized mainly by high expression of TIGIT, CD16, PRMT5, and SIGIRR; low expression of CD56, IFN-γ, and CD69; significantly decreased percentage of CD56 + NK cells; and significantly increased percentage of CD16 + CD56- NK cells with weakened killing ability. PRMT5 and TIGIT may be closely related to the formation of CD16 + CD56- NK cells with weakened killing ability.

Abstract Image

Abstract Image

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CD16 + CD56-自然杀伤细胞上高表达的PRMT5与结直肠癌间质NK细胞耗竭相关。
目的:探讨结直肠癌(CRC)微环境中自然杀伤细胞(NK细胞)表型变化与重要免疫检查点表达的关系。评估CD16亮CD56阴性(CD16 + CD56-) NK细胞相关免疫检查点,包括蛋白精氨酸甲基转移酶5 (PRMT5)和带有Ig和ITIM结构域的t细胞免疫受体(TIGIT)、单免疫球蛋白白介素-1相关受体(SIGIRR)在结直肠癌间质中的表达水平。方法:对194例确诊为结直肠癌的患者进行筛查。评估结直肠癌肿瘤微环境(TME)中NK细胞的百分比及其表面受体PRMT5、CD56、CD69、TIGIT、CD16、IFN-γ和SIGIRR的表达水平。进行免疫组织化学染色、多重免疫组织化学染色和单细胞测序。结果:与正常间质相比,结直肠癌间质中NK细胞较少。肿瘤间质中CD16 + CD56- NK细胞的比例明显较高,CD16 + NK细胞数量较多,CRC间质中CD56 + NK细胞数量较少。TIGIT和PRMT5的高表达影响结直肠癌的进展。PRMT5和SIGIRR的表达在CD16 + CD56- NK细胞中显著升高,这两个基因被认为是重要的发病因素。PRMT5和SIGIRR可能参与了CRC中NK细胞的表型改变。结论:结直肠癌微环境处于以TIGIT、CD16、PRMT5、SIGIRR高表达为主要特征的免疫抑制状态;CD56、IFN-γ、CD69低表达;CD56 + NK细胞百分比显著降低;杀伤能力减弱的CD16 + CD56- NK细胞比例显著增加。PRMT5和TIGIT可能与CD16 + CD56- NK细胞杀伤能力减弱的形成密切相关。
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来源期刊
CiteScore
10.50
自引率
1.70%
发文量
207
审稿时长
1 months
期刊介绍: Cancer Immunology, Immunotherapy has the basic aim of keeping readers informed of the latest research results in the fields of oncology and immunology. As knowledge expands, the scope of the journal has broadened to include more of the progress being made in the areas of biology concerned with biological response modifiers. This helps keep readers up to date on the latest advances in our understanding of tumor-host interactions. The journal publishes short editorials including "position papers," general reviews, original articles, and short communications, providing a forum for the most current experimental and clinical advances in tumor immunology.
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