The immunomodulatory effects of cannabidiol on Hsp70-activated NK cells and tumor target cells

IF 3.2 3区医学 Q2 BIOCHEMISTRY & MOLECULAR BIOLOGY

Molecular immunology Pub Date : 2024-08-09 DOI:10.1016/j.molimm.2024.07.008

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引用次数: 0

Abstract

Background

Cannabidiol (CBD), the major non-psychoactive component of cannabis, exhibits anti-inflammatory properties, but less is known about the immunomodulatory potential of CBD on activated natural killer (NK) cells and/or their targets. Many tumor cells present heat shock protein 70 (Hsp70) on their cell surface in a tumor-specific manner and although a membrane Hsp70 (mHsp70) positive phenotype serves as a target for Hsp70-activated NK cells, a high mHsp70 expression is associated with tumor aggressiveness. This study investigated the immuno-modulatory potential of CBD on NK cells stimulated with TKD Hsp70 peptide and IL-2 (TKD+IL-2) and also on HCT116 p53wt and HCT116 p53-/- colorectal cancer cells exhibiting high and low basal levels of mHsp70 expression.

Results

Apart from an increase in the density of NTB-A and a reduced expression of LAMP-1, the expression of all other activatory NK cell receptors including NKp30, NKG2D and CD69 which are significantly up-regulated after stimulation with TKD+IL-2 remained unaffected after a co-treatment with CBD. However, the release of major pro-inflammatory cytokines by NK cells such as interferon-γ (IFN-γ) and the effector molecule granzyme B (GrzB) was significantly reduced upon CBD treatment. With respect to the tumor target cells, CBD significantly reduced the elevated expression of mHsp70 but had no effect on the low basal mHsp70 expression. Expression of other NK cell ligands such as MICA and MICB remained unaffected, and the NK cell ligands ULBP and B7-H6 were not expressed on these target cells. Consistent with the reduced mHsp70 expression, treatment of both effector and target cells with CBD reduced the killing of high mHsp70 expressing tumor cells by TKD+IL-2+CBD pre-treated NK cells but had no effect on the killing of low mHsp70 expressing tumor cells. Concomitantly, CBD treatment reduced the TKD+IL-2 induced increased release of IFN-γ, IL-4, TNF-α and GrzB, but CBD had no effect on the release of IFN-α when NK cells were co-incubated with tumor target cells.

Conclusion

Cannabidiol (CBD) may potentially diminish the anti-tumor effectiveness of TKD+IL-2 activated natural killer (NK) cells.

查看原文本刊更多论文

大麻二酚对 Hsp70 激活的 NK 细胞和肿瘤靶细胞的免疫调节作用。

背景：大麻二酚（CBD）是大麻中的主要非精神活性成分，具有抗炎特性，但人们对 CBD 对活化的自然杀伤（NK）细胞和/或其靶点的免疫调节潜力知之甚少。虽然膜 Hsp70（mHsp70）阳性表型是 Hsp70 激活的 NK 细胞的靶标，但高 mHsp70 表达与肿瘤的侵袭性有关。本研究探讨了 CBD 对接受 TKD Hsp70 肽和 IL-2 （TKD+IL-2）刺激的 NK 细胞的免疫调节潜力，以及 CBD 对 mHsp70 高、低基础表达水平的 HCT116 p53wt 和 HCT116 p53-/- 大肠癌细胞的免疫调节潜力：除了NTB-A的密度增加和LAMP-1的表达量减少外，所有其他活化NK细胞受体（包括NKp30、NKG2D和CD69）的表达量在受到TKD+IL-2刺激后都会显著上调。然而，CBD 处理后，NK 细胞释放的主要促炎细胞因子，如干扰素-γ（IFN-γ）和效应分子颗粒酶 B（GrzB）的量明显减少。在肿瘤靶细胞方面，CBD 能明显降低 mHsp70 的高表达，但对 mHsp70 的低基础表达没有影响。其他 NK 细胞配体（如 MICA 和 MICB）的表达未受影响，NK 细胞配体 ULBP 和 B7-H6 也未在这些靶细胞上表达。与 mHsp70 表达减少一致的是，用 CBD 处理效应细胞和靶细胞会减少 TKD+IL-2+CBD 预处理 NK 细胞对高 mHsp70 表达肿瘤细胞的杀伤力，但对低 mHsp70 表达肿瘤细胞的杀伤力没有影响。同时，CBD 处理降低了 TKD+IL-2诱导的 IFN-γ、IL-4、TNF-α 和 GrzB 的释放增加，但当 NK 细胞与肿瘤靶细胞共培养时，CBD 对 IFN-α 的释放没有影响：结论：大麻二酚（CBD）可能会降低TKD+IL-2激活的自然杀伤（NK）细胞的抗肿瘤效果。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Molecular immunology 医学-免疫学

CiteScore

6.90

自引率

2.80%

发文量

324

审稿时长

50 days

期刊介绍： Molecular Immunology publishes original articles, reviews and commentaries on all areas of immunology, with a particular focus on description of cellular, biochemical or genetic mechanisms underlying immunological phenomena. Studies on all model organisms, from invertebrates to humans, are suitable. Examples include, but are not restricted to: Infection, autoimmunity, transplantation, immunodeficiencies, inflammation and tumor immunology Mechanisms of induction, regulation and termination of innate and adaptive immunity Intercellular communication, cooperation and regulation Intracellular mechanisms of immunity (endocytosis, protein trafficking, pathogen recognition, antigen presentation, etc) Mechanisms of action of the cells and molecules of the immune system Structural analysis Development of the immune system Comparative immunology and evolution of the immune system "Omics" studies and bioinformatics Vaccines, biotechnology and therapeutic manipulation of the immune system (therapeutic antibodies, cytokines, cellular therapies, etc) Technical developments.