Abstract
Cytotoxic T-lymphocyte-associated antigen-4 (CTLA-4) is a potent immunoregulatory molecule that downregulates T-cell activation and thus influences the antitumor immune response. CTLA-4 polymorphisms are associated with various cancers, and CTLA-4 mRNA/protein increased expression is found in several tumor types. However, most of the studies are based on peripheral blood mononuclear cells, and much less is known about the relationship between CTLA-4 expression, especially gene expression, and its polymorphic variants in cancer tissue. In our study we assessed the distribution of CTLA-4 two polymorphisms (+49A/G and −318C/T), using TaqMan probes (rs231775 and rs5742909, resp.), and CTLA-4 gene expression in real-time PCR assay in non-small-cell lung cancer (NSCLC) tissue samples. The increased CTLA-4 expression was observed in the majority of NSCLC patients, and it was significantly correlated with TT genotype (−318C/T) and with tumor size (T2 versus T3 + T4). The presence of G allele and GG genotype in cancer tissue (+49A/G) was significantly associated with the increased NSCLC risk. Additionally, we compared genotype distributions in the corresponding tumor and blood samples and found statistically significant differences. The shift from one genotype in the blood to another in the tumor may confirm the complexity of gene functionality in cancer tissue.
Highlights
The incidence and development of cancer are closely related to dysfunction of immune function
The first activating signal is delivered by the tumor-associated antigens (TAAs) displayed by major histocompatibility complex (MHC) class I molecules on antigenpresenting cells (APCs) [4, 5], and it provides specificity to the response
We focused on the associations between Cytotoxic T-lymphocyte-associated antigen-4 (CTLA-4) expression and gene polymorphic variants and nonsmall-cell lung cancer (NSCLC) patients characteristics, as well as tumor clinical staging
Summary
The incidence and development of cancer are closely related to dysfunction of immune function. Human can initiate immune response towards tumors by means of several different mechanisms. As cancer cells have developed multiple mechanisms to evade the immune response [3] proper function of cytotoxic T lymphocytes (CTLs) is critical for immunosurveillance. CTLs after activation are able to recognize and kill autologous cancer cells. The first activating signal is delivered by the tumor-associated antigens (TAAs) displayed by major histocompatibility complex (MHC) class I molecules on antigenpresenting cells (APCs) [4, 5], and it provides specificity to the response. The second, so-called the “costimulatory signal”, as it stimulates T cells in conjunction with antigen, is provided by molecules on APCs that engage particular costimulatory receptors on T cells. The best known is the CD28 receptor, which binds to two costimulatory molecules, B7-1 (CD80)
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