CTLA-4

Triple negative breast cancer TNBC is the type of breast cancer that does not have Estrogen receptor, Progesterone receptor and human epidermal growth factor receptors 2 (HER2) when stained with the Immunohistochemistry stains. As it's lacking the targets for most chemotherapy medications, it has a more aggressive course, a poor prognosis, higher chances of relapse and usually diagnosed at a later stage. In this review, we are illustrating how the immune system can be manipulated to attack the micro-environment that the cancer creates to escape and thrive. Also, we are discussing the signaling pathways of the immune system on which the immunotherapy medications were based and the different chemotherapy options that are used in the same regiment for management of TNBC.

Background: The Cytotoxic T lymphocyte antigen (CTLA-4) is one of the major susceptibility genes associated with autoimmune diseases. Susceptibility to rheumatoid arthritis (RA) is determined by both environmental and genetic factors. The genetic contribution approaches 50–60%. The association between RA with the + 49ANG CTLA-4 polymorphism in the Mexican population was investigated. Methods: The polymerase chain reaction–restriction fragment was used to amplify the + 49ANG CTLA-4 polymorphism in RA patients and healthy subjects (HS). Results: We analyzed the association between the + 49ANG CTLA-4 polymorphism and RA. The G allele frequency was higher in RA patients than HS (46.8 vs 37.7%, OR = 1.45, p = 0.01). RA patients carrying the A/G genotype were significantly more likely to be positive to CRP and RF. There was no evidence of an association between SNP genotypes and the clinical characteristics of rheumatoid arthritis. Conclusions: The +49ANG CTLA-4 polymorphism is a genetic marker of susceptibility for RA in western Mexican population.

Chagas disease affects approximately 10 million people mainly in Latin America. The immune regulation by the host seems to be an essential factor for disease evolution, and immune system inhibitory molecules such as CTLA-4 and PD-1 favor the maintenance of peripheral tolerance. Considering that polymorphisms at the immunoregulatory CTLA-4 and PDCD1 genes may alter their inhibitory function, we investigated the association of alleles, genotypes and haplotypes of polymorphic sites observed at the CTLA-4 and PDCD1 genes with different clinical manifestations of chronic Chagas disease (indeterminate, cardiac, digestive and mixed). The polymorphisms at the CTLA-4 (-1722T/C, -318C/T and +49A/G) and PDCD1 (PD-1.3G/A) genes were typed using TaqMan methodology in 277 chronic Chagas disease patients classified into four groups, according to clinical characteristics, and 326 non-infected controls. Our results showed that CTLA-4 -1722CC genotype (22%), -1722C allele (27%) and CTLA-4 TCG (8.6%), TCA (26%) and CCA (15%) haplotypes were strongly associated with the indeterminate form, while the CTLA-4 -318CT genotype (82%) and CTLA-4 -318T allele (47%) were found mainly in patients with the mixed form of the disease. The CTLA-4 TCG haplotype (10.2%) was associated with the digestive form. On the other hand, the PD-1.3G/A polymorphism was not associated with chronic Chagas disease and its clinical manifestations. Here, we showed that alleles, genotypes and haplotypes reported to increase the expression of the regulatory molecule CTLA-4 were associated with the indeterminate form of the disease. Taken together, our data support the idea that polymorphic sites at immunoregulatory genes may influence the development of Chagas disease variants.