27 research outputs found
The Role of Polymorphisms in Co-Signalling Molecules’ Genes in Susceptibility to B-Cell Chronic Lymphocytic Leukaemia
Tumour-infiltrating CD4 and CD8 T lymphocytes in breast cancer
Lymphocytes are cells circulating between the blood and tissues. It has been stated that a correlation exists between immune infiltrate and breast cancer. These tumours are infiltrated by T cells, B cells, natural killer cells and macrophages. The infiltrating T cells are of helper (CD4+) and cytotoxic (CD8+) phenotypes. Specific immunity mediated by cytolytic T lymphocytes is suspected of playing an anticancer role. It is widely known that regional lymph nodes are an important immunological defence or “barrier” against tumour expansion. Some authors have reported that in cancer patients natural killer (NK) cells and CD8+ T cells are diminished in regional lymph nodes, particularly those involved by the tumour.In the presented study the authors review current knowledge on this problem and the possibility of using successful immunotherapy with monoclonal antibodies for breast cancer
ICOS gene polymorphisms in B-cell chronic lymphocytic leukemia in the Polish population
There is strong evidence that altered immunological function entails an increased risk of B-cell chronic
lymphocytic leukemia (B-CLL). The main mechanism of an anti-tumor response depends on T-cell activation.
Unlike the constitutively expressed CD28, inducible costimulatory molecule (ICOS) is expressed on the T-cell
surface after activation. ICOS enhances all the basic T-cell responses to a foreign antigen, namely proliferation,
secretion of lymphokines, the upregulation of molecules that mediate cell-cell interaction, and effective help for
antibody secretion by B cells. ICOS is essential for both efficient interaction between T and B cells and normal
antibody responses to T cell-dependent antigens. It does not upregulate the production of interleukin-2, but
superinduces the synthesis of interleukin-10. Our previous results indicated the ICOS gene has a role as a susceptibility
locus to B-CLL. Therefore an extended study was undertaken to evaluate the association between four
ICOS polymorphisms (which were recently described as functional ones) and susceptibility to B-CLL in the
Polish population. A case-control study of 296 individuals, including 146 B-CLL patients, was conducted on four
polymorphisms in the ICOS gene. Genotyping of the polymorphisms ICOS ISV1+173T>C (rs10932029),
ICOSc.1624C>T (rs10932037), ICOSc.2373G>C (rs4675379), and ICOSc.602A>C (rs10183087) was carried
out using allelic discrimination methods with the TaqMan® SNP Genotyping Assay. There were no statistically
significant differences in the allele, genotype, or haplotype distributions between B-CLL patients and healthy
controls for any of the investigated polymorphic markers in the ICOS gene. However, we noted that patients
carrying genotype ICOS ISV1+173T>C [TT], ICOSc.602A>C [AA], ICOSc.1624C>T [CC], and ICOSc.2373G>C
[GG] have a decreased frequency of progression to a higher Rai stage during 60-month follow-up (21.35% vs.
40.8%, p = 0.013) compared to other individuals. This indicates that the investigated polymorphisms do not modulate
the risk of B-CLL in the Polish population, but are associated with disease dynamics, in particular with the time
to Rai stage progression. (Folia Histochemica et Cytobiologica 2011; Vol. 49, No. 1, pp. 49–54
Dysregulated Expression of Both the Costimulatory CD28 and Inhibitory CTLA-4 Molecules in PB T Cells of Advanced Cervical Cancer Patients Suggests Systemic Immunosuppression Related to Disease Progression
Cervical cancer (CC) occurs more frequently in women who are immunosuppressed, suggesting that both local and systemic immune abnormalities may be involved in the evolution of the disease. Costimulatory CD28 and inhibitory CTLA-4 molecules expressed in T cells play a key role in the balanced immune responses. There has been demonstrated a relation between CD28, CTLA-4, and IFN genes in susceptibility to CC, suggesting their importance in CC development. Therefore, we assessed the pattern of CD28 and CTLA-4 expression in T cells from PB of CC patients with advanced CC (stages III and IV according to FIGO) compared to controls. We also examined the ability of PBMCs to secrete IFN-gamma. We found lower frequencies of freshly isolated and ex vivo stimulated CD4 + CD28+ and CD8 + CD28+ T cells in CC patients than in controls. Loss of CD28 expression was more pronounced in the CD8+ T subset. Markedly increased proportions of CTLA-4+ T cells in CC patients before and after culture compared to controls were also observed. In addition, patients’ T cells exhibited abnormal kinetics of surface CTLA-4 expression, with the peak at 24 h of stimulation, which was in contrast to corresponding normal T cells, revealing maximum CTLA-4 expression at 72 h of stimulation. Of note, markedly higher IFN-gamma concentrations were shown in supernatants of stimulated PBMCs from CC patients. Conclusions: Our report shows the dysregulated CD28 and CTLA-4 expression in PB T cells of CC patients, which may lead to impaired function of these lymphocytes and systemic immunosuppression related to disease progression
Variations in Suppressor Molecule CTLA-4 Gene Are Related to Susceptibility to Multiple Myeloma in a Polish Population
Various phenotype and functional T-cell abnormalities are observed in multiple myeloma (MM) patients. The aim of this study was to investigate the association between polymorphisms in the gene encoding cytotoxic T-lymphocyte antigen-4 (CTLA-4), a negative regulator of the T-lymphocyte immune response and susceptibility to multiple myeloma in a Polish population. Two hundred MM patients and 380 healthy subjects were genotyped for the following polymorphisms: CTLA-4c.49A>G, CTLA-4g.319C>T, CTLA-4g.*642AT(8_33), CT60 (CTLA-4g.*6230G>A), Jo31 (CTLA-4g.*10223G>T). Our study is the largest and most comprehensive evaluation to date of the association between genetic polymorphisms in the CTLA-4 molecule and multiple myeloma. It was found that CTLA-4c.49A>G[G], CT60[G], and Jo31[G] alleles were more frequently observed in MM patients than in controls (0.50 vs. 0.44, p = 0.03, 0.65 vs. 0.58, p = 0.04, and 0.63 vs. 0.57, p = 0.03, respectively). Moreover, the haplotype CTLA-4c.49A>G[G], CTLA-4g.319C>T[C], CTLA-4g.*642AT(8_33) [8], CT60[G], Jo31[G] including all susceptibility alleles increases the risk of MM about fourfold (OR: 3.79, 95%CI: 2.08–6.89, p = 0.00001). These findings indicate that genetic variations in the CTLA-4 gene play role in susceptibility to multiple myeloma and warrant further investigation through replication studies