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Review
. 2022 Nov 7:12:1019153.
doi: 10.3389/fonc.2022.1019153. eCollection 2022.

V体育平台登录 - Relationship between copper and immunity: The potential role of copper in tumor immunity

Fu Cheng  1   2 , Geng Peng  1   2 , Yan Lu  1   2 , Kang Wang  1   2 , Qinuo Ju  1   3 , Yongle Ju  1   2 , Manzhao Ouyang  1   2
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Review

VSports最新版本 - Relationship between copper and immunity: The potential role of copper in tumor immunity

Fu Cheng et al. Front Oncol. .

V体育官网入口 - Abstract

Copper is an essential trace element in an organism, and changes in copper levels in vivo often indicate a diseased state VSports手机版. Copper and immunity have been discussed since the last century, with copper deficiency significantly affecting the development and function of the immune system, such as increased host susceptibility to various pathogens, decreased number and impaired function of neutrophils, reduced antibacterial activity of macrophages, decreased proliferation of splenocytes, impaired B cell ability to produce antibodies and impaired function of cytotoxic T lymphocyte and helper T cells. In the past 20 years, some studies have shown that copper ions are related to the development of many tumors, including lung cancer, acute lymphoid leukaemia, multiple myeloma and other tumors, wherein copper ion levels were significantly elevated, and current studies reveal that copper ions are involved in the development, growth and metastasis of tumors through various pathways. Moreover, recent studies have shown that copper ions can regulate the expression of PD-L1, thus, attention should be paid to the important role of copper in tumor immunity. By exploring and studying copper ions and tumor immunity, new insights into tumor immunity could be generated and novel therapeutic approaches to improve the clinical prognosis of patients can be provided. .

Keywords: CTR-1; IL-2; PD-L1; copper chelators; copper deficiency; copper ionophores; tumor immunity. V体育安卓版.

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Conflict of interest statement

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Figures

Figure 1
Figure 1
The effects of copper deficiency on mice are divided into eight primary aspects: (i) reduced antibody secretion by B cells; (ii) reduced IL-2 secretion by helper T cells; (iii) reduced target cell killing capacity of cytotoxic T lymphocyte (CTL); (iv) reduced number of neutrophils and production of superoxide anion (O2-); (v) reduced responsiveness of lymphocytes to mitogen stimulation; (vi) thymic atrophy; (vii) splenomegaly and (viii) decreased ceruloplasmin(CP).
Figure 2
Figure 2
Copper plays an important role in extracellular matrix (ECM) construction and epithelial-mesenchymal transition (EMT), which are two key aspects of tumor metastasis. Copper promotes the secretion of LOX by tumor cells but inhibits the degradation of the structural stability of HIF-1α. There also exists a reciprocal relationship between LOX and HIF-1α. LOX promotes ECM formation by facilitating the cross-linking of collagen and elastin. Increased HIF-1α promotes the adaptation of tumor cells to the hypoxic environment while promoting EMT through interactions with the hypoxia response element (HRE) and the HIF1-α-Snail/Twist signaling pathway. Together, these factors promote the development of tumor metastasis.
Figure 3
Figure 3
Copper has been shown to promote tumor formation by affecting the regulation of phosphorylation in the PI3K-AKT and RAS-RAF-MEK-ERK signaling pathways, which in turn promotes tumor formation. Meanwhile, copper can regulate PD-L1 expression by both regulating the proteasome-mediated degradation of PD-L1 and affecting the transcription of PD-L1, which leads to tumor immune escape. In contrast, copper chelators can inhibit the aforementioned signaling pathways, thereby suppressing pro-tumor signaling and ameliorating tumor immune escape. cuprotosis is a recently identified copper-dependent mode of cell death, mainly through direct binding of copper to lipid acylated components of the TCA cycle, leading to lipid acyl protein aggregation and loss of iron-sulfur cluster proteins, which in turn leads to cuprotosis due to proteotoxic stress. These theoretical results have contributed to the understanding of the relationship between copper and tumors.
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