In the intracellular environment, zinc interacts with signal transducers implicated in immune response and influences both the structural stability and function of immunologically relevant transcription factors [3].
T-bet (Tbx21) is a T-box transcription factor family member that regulates the differentiation and function of immune cells.
This transcription factor plays an important role in the development and function of immune regulatory T cells (Tregs), and can be used as a specific biomarker for the identification of Tregs within an inflammatory infiltrate [ 2].
Within the immune suppressive tumor microenvironment, T cells acquire an "exhausted" phenotype, which is characterized by progressive loss of effector functions, changes in expression and function of key transcription factors, and metabolic alterations.
Diverse chemicals can impair functioning of the immune system.
For example, in higher gnathostomes like mammals the transcription factor Foxp3 controls the differentiation and function of regulatory T cells (Treg) specialized in enforcing self-tolerance in the mature immune system [8], [9], [10].
This is a function of the adaptive immune system.
Moreover, this transcription factor is a crucial regulator of the fate and function of dendritic cells (DCs) [ 69] that connect innate and acquired immune responses.
Given that TNBC has been recently categorised based on 6 molecular subtypes [30], the immunomodulatory (IM) subtype, characterised by elevated expression of genes involved in T-cell function, immune transcription, interferon (IFN) response and antigen processing, could benefit from immunotherapies.
Activation of Imd pathway leads to transcription of several other genes; many of them with unknown functions and which could be involved in the regulation and execution of the immune response [7].
In addition to genes primarily involved in functions of the human immune or sensory systems, signal transduction and metabolism, genes involved in transcription regulation, neurotransmitter transport, cell proliferation and differentiation or development were also identified (Table 1).
