Abstract
Immune system dysfunction is one of the key features in onset and development of cancer and autoimmunity. Cytotoxic T-lymphocyte-antigen-4 (CTLA-4), as a leader immune checkpoint plays a crucial effects in the regulation of immune suppression and tolerance. In this review, role of CTLA-4 and its three important polymorphisms (SNP), CTLA-4 +49A/G, CTLA-4 CT60 A/G and CTLA-4 −318C/T in development of cancer and autoimmune diseases have been discussed. The evidences revealed that CTLA-4 +49A/G, A allele increases the risk of cervical cancer and CTLA-4 +49A/G G allele decreases the risk of breast cancer in Asian population. The presence of G allele of CTLA-4 +49A/G SNP is strongly correlates with increased risk of Graves and systemic lupus erythematous (SLE), in Asian and European population. G allele of CTLA-4 +49A/G SNP may be a risk factor for rheumatoid arthritis susceptibility (RA). Evidence suggests that the presence of CTLA-4 +49 G allele reduces the inhibitory function of CTLA-4 on T cells. Therefore, it is logical to propose that G allele of CTLA-4 +49 A/G increases the immune system activity and decreases the risk of cancer. The evidence on the effect of CTLA-4 CT60 A/G SNP on the risk of cancer development and autoimmune disorders is inconclusive. No association was found between the CTLA-4 −318C/T polymorphism with autoimmune diseases.
Highlights
Immune system dysfunction is one of the key features in onset and development of cancer and autoimmunity [1]
cytotoxic T-lymphocyte antigen-4 (CTLA-4) serves as a negative regulator when it is associated with Treg cells and present antigen to T cells when they are expressed by antigen presenting cells [12]
We suggest that G allele of CTLA-4 +49 A/G may exacerbate conditions in which the immune response against foreign antigen will increase
Summary
Immune system dysfunction is one of the key features in onset and development of cancer and autoimmunity [1]. T cell activation and excessive expansion of activated T cells is inhibited by negative signals provided by immune checkpoints, cytotoxic T-lymphocyte antigen-4 (CTLA-4) and programmed death 1 (PD-1) [9]. Both CD28 and CTLA-4 receptors bind to CD80 and CD86 with different affinity. Despite many findings (information) regarding mechanisms by which CTLA-4 regulates T cell response, several studies suggest that genetic factors are involved in susceptibility to autoimmune diseases and malignancy [23,24,25,26]. In this mini-review, the mechanism by which CTLA-4 regulates T cell response and the effect of its gene mutations as associated with autoimmune and cancer susceptibility will be discussed
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