关键词: Colorectal cancer Granzyme B Interferon-γ secretion Natural killer cells Perforin Tumor stage

Mesh : Humans Killer Cells, Natural / immunology metabolism Colorectal Neoplasms / immunology pathology metabolism blood Male Female Middle Aged Interferon-gamma / metabolism Aged Granzymes / metabolism Perforin / metabolism CD56 Antigen / metabolism Flow Cytometry Adult

来  源:   DOI:10.1038/s41598-024-63103-x   PDF(Pubmed)

Abstract:
Natural killer (NK) cells are closely associated with malignant tumor progression and metastasis. However, studies on their relevance in colorectal cancer (CRC) are limited. We aimed to comprehensively analyze the absolute counts, phenotypes, and function of circulating NK cells in patients with CRC using multiparametric flow cytometry. The distribution of NK cell subsets in the peripheral circulation of patients with CRC was significantly altered relative to the control group. This is shown by the decreased frequency and absolute count of CD56dimCD16+ NK cells with antitumor effects, contrary to the increased frequency of CD56bright NK and CD56dimCD16- NK cells with poor or ineffective antitumor effects. NK cells in patients with CRC were functionally impaired, with decreased intracellular interferon (IFN)-γ secretion and a significantly lower percentage of cell surface granzyme B and perforin expression. In addition, IFN-γ expression decreased significantly with the tumor stage progression. Based on a comprehensive analysis of the absolute counts, phenotypes, and functional markers of NK cells, we found an altered subset distribution and impaired function of circulating NK cells in patients with CRC.
摘要:
自然杀伤(NK)细胞与恶性肿瘤的进展和转移密切相关。然而,关于它们与结直肠癌(CRC)相关性的研究有限。我们旨在全面分析绝对计数,表型,使用多参数流式细胞术检测CRC患者循环NK细胞的功能。与对照组相比,CRC患者外周血中NK细胞亚群的分布显着改变。这可以通过具有抗肿瘤作用的CD56dimCD16+NK细胞的频率和绝对计数的降低来证明。与CD56brightNK和CD56dimCD16-NK细胞的频率增加相反,抗肿瘤作用较差或无效。CRC患者的NK细胞功能受损,细胞内干扰素(IFN)-γ分泌减少,细胞表面颗粒酶B和穿孔素表达的百分比显着降低。此外,IFN-γ表达随肿瘤分期进展而显著下降。根据对绝对计数的综合分析,表型,和NK细胞的功能标记,我们发现CRC患者的循环NK细胞亚群分布和功能受损.
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