Inflammation and immune evasion are major key players in breast cancer (BC) progression. Recently, the FDA approved the use of anti-programmed death-ligand 1 antibody (anti-PD-L1) and phosphoinositide 3-kinase (PI3K) inhibitors against aggressive BC. Despite the paradigm shift in BC treatments, patients still suffer from resistance, recurrence and serious immune-related adverse events. These obstacles require unravelling of the hidden molecular contributors for such therapy failure hence yielding therapeutics that are at least as efficient yet safer. Inflammasome pathway is activated when the pattern recognition receptor senses danger signals (danger-associated molecular patterns) from damagedRdying cells or pathogen-associated molecular patterns found in microbes, leading to secretion of the active pro-inflammatory cytokines interleukin-1β (IL-1β) and interleukin-18 (IL-18). It has been shown throughout numerous studies that inflammasome pathway enhanced invasion, metastasis, provoked BC progression and therapy resistance. Additionally, inflammasomes upregulated the proliferative index ki67 and enhanced PD-L1 expression leading to immunotherapy resistance. IL-1β contributed to significant decrease in oestrogen receptor levels and promoted BC chemo-resistance. High levels of IL-18 in sera of BC patients were associated with worst prognosis. Stimulation of purinergic receptors and modulation of adipokines in obese subjects activated inflammasomes that evoked radiotherapy resistance and BC progression. The micro RNA miR-223-3p attenuated the inflammasome over-expression leading to lowered tumour volume and lessened angiogenesis in BC. This review sheds the light on the molecular pathways of inflammasomes and their impacts in distinct BC subtypes. In addition, it highlights novel strategies in treatment and prevention of BC.

Pregnancy is considered a period in which immunomodulation occurs, although it is important for the maintenance of the foetus, could contribute to infections as Toxoplasma gondii. Immune response cells such as regulatory T cells participate in this immunomodulation, and surface molecules such as CTLA-4 develop an immunosuppressive role, could contribute to the establishment of the parasite. This study aimed to evaluate the presence of regulatory T cells and the expression of CTLA-4 in parturient and non-pregnant seropositive and seronegative for anti-T. gondii antibodies. Sixty-two participants were evaluated, 14 parturient with negative serology, 23 parturient with positive serology, 16 non-pregnant women seronegative and 9 non-pregnant women seropositive. Immunophenotyping was performed for characterize TCD4+Foxp3+ cells, T CD4+CD25-Foxp3+, TCD4+CD25highFoxp3+, TCD4+CTLA-4+, TCD4+CD25-CTLA-4+ and TCD4+CD25highCTLA-4+. We observed a lower level of CD4+CD25highFoxp3+ cells from seropositive parturient compared with seropositive non-pregnant cells. Significative levels of CD4+CD25-Foxp3+ cells from seronegative pregnant were observed compared with seropositive pregnant cells. Furthermore, the higher level of CD4+CD25-CTLA-4+ cells populations was detected in seropositive pregnant cells compared with seropositive non-pregnant. Although a significant increase in CTLA-4 cells was observed in pregnant women positive for anti-T. gondii antibodies, this increase did not cause a risk of reactivation of the infection.

Several genetic loci appear to be involved in susceptibility to autoimmune disease. Some loci are disease specific, whereas others appear to exert a general effect on the autoimmune disease process. Despite a large number of studies of many different diseases, consistent associations with multiple autoimmune disorders have been restricted to three gene regions: the human leukocyte antigen (HLA) class II region on chromosome 6p21, the gene encoding cytotoxic T lymphocyte-associated 4 (CTLA-4) on chromosome 2q33, and the PTPN22 gene encoding lymphoid tyrosine phosphatase (LYP) on chromosome 1p13. Each of these loci is likely to encode molecules that are crucial in the immune cascade and are actively involved in T-cell activation. Moreover, gene polymorphisms that affect function might contribute to the triggering of autoimmune disease by as-yet-unknown mechanisms. This review summarises recent developments and current understanding of the way in which molecules encoded by these susceptibility loci contribute to T-cell activation, and hypothesises how aberrant function of these molecules might trigger autoimmunity.

Type 1 diabetes mellitus (IDDM) results from a chronic process of autoimmune destruction of ß cells of the Langerhans islets. The presence of autoantibodies (ICA, GADA, anti-IA2, IAA) in serum preceds the clinical onset of the disease. Genetic predisposition for IDDM is connected with HLA, CTLA-4 and insulin gene region.

The aim of the study was the genetic and immunological analysis of a triplet. One of them developed Type 1 diabetes mellitus. We analysed HLA class II, CTLA-4 and insulin gene polymorphisms in the whole family. Besides, we investigated immunological status of three brothers.

All patients present identical genotype for VNTR loci: D1S80, D17S5 and Apo B, as well as for HLA-DRB1, — DQA1, — DQB1, CTLA-4 gene and all studied insulin gene polymorphisms. That proves their monozigosity. The triplet presents strong genetic predisposition for IDDM. The two patients without overt diabetes have increased levels of ICA, GADA, IA2 and IAA.