Your browser doesn't support javascript.
loading
Show: 20 | 50 | 100
Results 1 - 3 de 3
Filter
Add more filters










Database
Language
Publication year range
1.
J Immunol Res ; 2020: 6545921, 2020.
Article in English | MEDLINE | ID: mdl-32775467

ABSTRACT

Chronic lymphocytic leukemia (CLL) is characterized by the peripheral accumulation of neoplastic B cells and is frequently complicated by the systemic immunosuppression associated with an impairment in B and T lymphocyte activation. We hypothesized that the expression of immune checkpoint suppressors B and T lymphocyte attenuator (BTLA) and cytotoxic T lymphocyte antigen (CTLA-4) is disturbed in both lymphocyte subpopulations in CLL. The expression of CTLA-4 and BTLA mRNA was determined by real-time PCR, while CTLA-4 protein expression (surface or intracellular) was estimated in BTLA+ lymphocytes by flow cytometry. In CLL patients, we observed a higher gene transcript level of BTLA and CTLA-4 than in healthy individuals in both freshly isolated and PMA stimulated B and T cells. Remarkably, lower amounts of both inhibitory proteins were found in peripheral blood (PB) CLL B cells, whereas normal BTLA and elevated CTLA-4 were found in T cells. Consistently, there was a prevalence of CTLA-4+ cells within circulating BTLA+ T cells cells of patients confronting PB healthy cells. After in vitro stimulation, the only change found in CLL patients was a decrease in BTLA expression in B and T lymphocytes. In contrast, healthy lymphocytes responded more vigorously as regards the BTLA and CTLA expression with substantially higher frequency of CD69+ cells under the stimulating condition compared to corresponding cells from the CLL group. Our results indicate that CLL development is associated with the affected expression of BTLA and CTLA-4 checkpoint receptors in PB and its impaired expression might be associated with lowering of the threshold for B cell activation and proliferation, while upregulated CTLA-4 expression in CLL peripheral BTLA+ T cells may contribute to suppressed T cell effector functions. This hypothesis needs to be validated in future studies, which would allow us to explain how the increased or decreased expression of these molecules affects the cell function.


Subject(s)
CTLA-4 Antigen/metabolism , Immune Checkpoint Proteins/metabolism , Leukemia, Lymphocytic, Chronic, B-Cell/metabolism , Receptors, Immunologic/metabolism , Adult , Aged , Antigens, CD/metabolism , Antigens, Differentiation, T-Lymphocyte/metabolism , B-Lymphocytes/metabolism , Cell Proliferation/physiology , Cells, Cultured , Female , Humans , Lectins, C-Type/metabolism , Leukocytes, Mononuclear/metabolism , Lymphocyte Activation/physiology , Male , Middle Aged , RNA, Messenger/metabolism , T-Lymphocytes/immunology , Up-Regulation/physiology
2.
Pathol Oncol Res ; 23(4): 837-843, 2017 Oct.
Article in English | MEDLINE | ID: mdl-28101800

ABSTRACT

The impairment of immunological surveillance caused by aberrant T cell activation can lead to an inadequate anti-tumor response. Therefore, deregulation in co-stimulatory pathway might be associated with cancer susceptibility. Here we undertook a prospective study to investigate whether genetic variations in gene encoding molecule CD28 and CTLA-4 playing pivotal role in regulating adoptive immune response can influence susceptibility to prostate cancer. Single nucleotide polymorphisms (SNPs) in CTLA-4 and CD28 genes were genotyped in 301 prostate cancer (PCa) patients and 301 controls. The distributions of the genotypes and haplotypes in the CTLA-4/CD28 SNPs were similar in both studied groups. However, the overrepresentation of carriers of CTLA-4c.49A>G[A] allele and carriers of CTLA-4g.319C>T[T] allele in PCa as compared to controls was observed (p = 0.082 and p = 0.13, respectively). The risk of disease was higher (OR 1.78) for carriers of both susceptibility alleles as compared to carriers of protective genotypes (p = 0.03). The CTLA-4c.49A>G and CTLA-4g.319C>T SNPs might be considered as low risk susceptibility locus for PCa.


Subject(s)
CD28 Antigens/genetics , CTLA-4 Antigen/genetics , Genetic Predisposition to Disease/genetics , Prostatic Neoplasms/genetics , Prostatic Neoplasms/immunology , Genotype , Humans , Male , Middle Aged , Polymorphism, Single Nucleotide , Risk Factors
3.
Tissue Antigens ; 85(6): 466-75, 2015 Jun.
Article in English | MEDLINE | ID: mdl-25855135

ABSTRACT

Human leukocyte antigen-G (HLA-G) is a nonclassical HLA class I molecule absent from most normal tissues but detected in many malignant tumors. It is recognized by cells of the immune system using LILRB1, KIR2DL4 and LILRB2 receptors. We attempted to find out whether some polymorphisms of HLA-G, LILRB1 and KIR2DL4 genes are associated with susceptibility to nonsmall cell lung cancer (NSCLC). Four polymorphisms in HLA-G, i.e. -964A>G (rs1632947), -725C>G>T (rs1233334), -716T>G (rs2249863) in the promoter, and a 14 base pair insertion/deletion (14 bp indel) in the 3'-untranslated region (3'UTR), and five in LILRB1 - 5651G>A (rs41308748) in intron 14, 5717C>T L622L (rs1061684), 5724G>A E625K (rs16985478), 5774 C>A P641P (rs41548213) in exon 15, and 5806C>T (rs8101240) in 3'UTR - as well as 9620 9A/10A (rs11410751) polymorphism in exon 7 of KIR2DL4 were typed using different laboratory techniques. Only one single nucleotide polymorphism (SNP) in HLA-G (-964A>G) and one in LILRB1 (5724G>A) were found to influence the risk of NSCLC. In addition, 5724G>A was associated with protection from tumor cell infiltration of regional lymph nodes. Most importantly, we detected HLA-G and LILRB1 expression in tumor specimens, but no correlation with genetic polymorphisms was observed. HLA-G and LILRB1 protein expression levels in tumor tissue were significantly correlated with tumor stage.


Subject(s)
Antigens, CD/genetics , Antigens, Neoplasm/genetics , Carcinoma, Non-Small-Cell Lung/genetics , HLA-G Antigens/genetics , INDEL Mutation , Lung Neoplasms/genetics , Neoplasm Proteins/genetics , Polymorphism, Single Nucleotide , Receptors, Immunologic/genetics , Receptors, KIR2DL4/genetics , Adolescent , Adult , Aged , Aged, 80 and over , Amino Acid Substitution , Antigens, CD/biosynthesis , Antigens, CD/immunology , Antigens, Neoplasm/biosynthesis , Antigens, Neoplasm/immunology , Biomarkers, Tumor , Carcinoma, Non-Small-Cell Lung/epidemiology , Carcinoma, Non-Small-Cell Lung/pathology , Female , Gene Expression Profiling , Gene Frequency , HLA-G Antigens/biosynthesis , HLA-G Antigens/immunology , Humans , Leukocyte Immunoglobulin-like Receptor B1 , Lung Neoplasms/epidemiology , Lung Neoplasms/pathology , Lymphatic Metastasis , Male , Middle Aged , Neoplasm Invasiveness , Neoplasm Proteins/biosynthesis , Neoplasm Proteins/immunology , Neoplasm Staging , Promoter Regions, Genetic/genetics , Receptors, Immunologic/biosynthesis , Receptors, Immunologic/immunology , Receptors, KIR2DL4/biosynthesis , Receptors, KIR2DL4/immunology , Risk , Young Adult
SELECTION OF CITATIONS
SEARCH DETAIL
...