Other search tools

About this data

The publication data currently available has been vetted by Vanderbilt faculty, staff, administrators and trainees. The data itself is retrieved directly from NCBI's PubMed and is automatically updated on a weekly basis to ensure accuracy and completeness.

If you have any questions or comments, please contact us.

Results: 1 to 10 of 19

Publication Record

Connections

Biomarkers for assessing the effectiveness of immunotherapy in breast cancer.
Nixon MJ, Balko JM
(2018) Biomark Med 12: 97-100
MeSH Terms: B7-H1 Antigen, Biomarkers, Tumor, Breast Neoplasms, CTLA-4 Antigen, Female, Humans, Immunotherapy, Ipilimumab, Triple Negative Breast Neoplasms
Added March 14, 2018
0 Communities
1 Members
0 Resources
9 MeSH Terms
Cytotoxic T-lymphocyte antigen-4 single nucleotide polymorphisms are not associated with outcomes after unrelated donor transplantation: a center for international blood and marrow transplant research analysis.
Sengsayadeth S, Wang T, Lee SJ, Haagenson MD, Spellman S, Fernandez Viña MA, Muller CR, Verneris MR, Savani BN, Jagasia M
(2014) Biol Blood Marrow Transplant 20: 900-3
MeSH Terms: Adolescent, Adult, Aged, CTLA-4 Antigen, Female, Hematopoietic Stem Cell Transplantation, Humans, Leukemia, Myeloid, Acute, Male, Middle Aged, Multivariate Analysis, Myelodysplastic Syndromes, Polymorphism, Single Nucleotide, Treatment Outcome, Unrelated Donors, Young Adult
Show Abstract · Added March 20, 2014
Cytotoxic T-lymphocyte antigen-4 (CTLA-4) plays an essential role in T cell homeostasis by restraining immune responses. AG and GG genotypes of donor CTLA-4 SNP rs4553808 in patients after unrelated donor hematopoietic stem cell transplantations (HSCT) have been shown to be an independent predictor of inferior relapse-free survival (RFS) and overall survival (OS) compared with those with the AA genotype, in single-center studies. We tested the hypothesis that SNP rs4553808 is associated with RFS, OS, nonrelapse mortality (NRM) and the cumulative incidence of acute graft-versus-host disease (GVHD) and chronic GVHD in adults with acute myeloid leukemia and advanced myelodysplastic syndrome undergoing a first 8/8 or 7/8 HLA-matched unrelated donor HSCT. Multivariable analysis adjusting for relevant donor and recipient characteristics showed no significant association between SNP rs4553808 and OS, RFS, NRM, and incidence of acute and chronic GVHD. An exploratory analysis of other CTLA-4 SNPs, as well as studying the interaction with antithymocyte globulin, also demonstrated no significant associations. Our results indicate that CTLA-4 SNPs are not associated with HSCT outcomes.
Published by Elsevier Inc.
0 Communities
1 Members
0 Resources
16 MeSH Terms
In vitro induction of regulatory CD4+CD8α+ T cells by TGF-β, IL-7 and IFN-γ.
Van Kaer L, Rabacal WA, Scott Algood HM, Parekh VV, Olivares-Villagómez D
(2013) PLoS One 8: e67821
MeSH Terms: Adoptive Transfer, Animals, Antigens, CD, Antigens, Differentiation, CD4 Antigens, CD8 Antigens, CTLA-4 Antigen, Cell Differentiation, Cell Lineage, Core Binding Factor Alpha 3 Subunit, Cytokines, Immunophenotyping, Interferon-gamma, Interleukin-7, Intestinal Mucosa, Mice, Mice, Knockout, NK Cell Lectin-Like Receptor Subfamily K, Programmed Cell Death 1 Receptor, T-Lymphocytes, Regulatory, Transforming Growth Factor beta, Vitamin D
Show Abstract · Added March 7, 2014
In vitro CD4(+) T cell differentiation systems have made important contributions to understanding the mechanisms underlying the differentiation of naive CD4(+) T cells into effector cells with distinct biological functions. Mature CD4(+) T cells expressing CD8αα homodimers are primarily found in the intestinal mucosa of men and mice, and to a lesser extent in other tissues such as peripheral blood. Although CD4(+)CD8α(+) T cells are easily identified, very little is known about their development and immunological functions. It has been reported, however, that CD4(+)CD8α(+) T cells possess regulatory properties. In this report, we present a novel in vitro differentiation system where CD4(+) T cells are stimulated to become CD4(+)CD8α(+) T cells in the presence of TGF-β, IL-7 and IFN-γ, resulting in cells with very similar features as CD4(+)CD8α(+) intraepithelial lymphocytes. This novel in vitro differentiation culture should provide a powerful and tractable tool for dissecting the differentiation and biological functions of CD4(+)CD8α(+) T cells.
0 Communities
3 Members
0 Resources
22 MeSH Terms
Genetic variation in donor CTLA-4 regulatory region is a strong predictor of outcome after allogeneic hematopoietic cell transplantation for hematologic malignancies.
Jagasia M, Clark WB, Brown-Gentry KD, Crawford DC, Fan KH, Chen H, Kassim A, Greer JP, Engelhardt BG, Savani BN
(2012) Biol Blood Marrow Transplant 18: 1069-75
MeSH Terms: Adolescent, Adult, Aged, CTLA-4 Antigen, Female, Graft vs Tumor Effect, Hematologic Neoplasms, Hematopoietic Stem Cell Transplantation, Humans, Male, Middle Aged, Polymorphism, Single Nucleotide, Risk Factors, Secondary Prevention, Survival Analysis, T-Lymphocytes, Cytotoxic, Tissue Donors, Transplantation, Homologous, Treatment Outcome
Show Abstract · Added December 10, 2013
Relapse remains a major cause of death after allogeneic hematopoietic cell transplantation (allo-HCT). Graft-versus-tumor effect is primarily mediated by donor T cells. Cytotoxic T lymphocyte antigen-4 (CTLA-4) is a critical inhibitor of T cell proliferation. Single nucleotide polymorphisms (SNPs) in CTLA-4 may affect immune responses. We hypothesized that CTLA-4 SNPs will be associated with disease control after allo-HCT. One hundred sixty-four adult patients with the availability of pretransplantation recipient and donor DNA samples were included in this analysis. Ten tagSNPs of the CTLA-4 gene were identified. Donor CTLA-4 SNP rs4553808 was associated with decreased relapse-free survival (RFS) (P = .019) and overall survival (OS) (P = .033). In multivariable analysis of an additive genetic model, genotype of CTLA-4 SNP rs4553808 was an independent risk factor for inferior RFS (hazard ratio [HR] = 1.73, 95% confidence interval [CI] 1.10-2.71, P = .017) and OS (HR = 1.84, 95% CI 1.13-3.0, P = .015). CTLA-4 SNPs can be used to identify high-risk patient subsets that may benefit from preemptive immunomodulation to decrease relapse rates and improve survival.
Copyright © 2012 American Society for Blood and Marrow Transplantation. Published by Elsevier Inc. All rights reserved.
0 Communities
3 Members
0 Resources
19 MeSH Terms
Genetics and the environment converge to dysregulate N-glycosylation in multiple sclerosis.
Mkhikian H, Grigorian A, Li CF, Chen HL, Newton B, Zhou RW, Beeton C, Torossian S, Tatarian GG, Lee SU, Lau K, Walker E, Siminovitch KA, Chandy KG, Yu Z, Dennis JW, Demetriou M
(2011) Nat Commun 2: 334
MeSH Terms: Animals, Antigens, CD, CTLA-4 Antigen, Case-Control Studies, Cholecalciferol, Cohort Studies, Down-Regulation, Female, Genetic Variation, Glycosylation, Haplotypes, Humans, Male, Mice, Mice, Inbred Strains, Multiple Sclerosis, N-Acetylglucosaminyltransferases, Receptors, Interleukin-2, Receptors, Interleukin-7, Risk Factors, Signal Transduction, Sunlight
Show Abstract · Added November 15, 2013
How environmental factors combine with genetic risk at the molecular level to promote complex trait diseases such as multiple sclerosis (MS) is largely unknown. In mice, N-glycan branching by the Golgi enzymes Mgat1 and/or Mgat5 prevents T cell hyperactivity, cytotoxic T-lymphocyte antigen 4 (CTLA-4) endocytosis, spontaneous inflammatory demyelination and neurodegeneration, the latter pathologies characteristic of MS. Here we show that MS risk modulators converge to alter N-glycosylation and/or CTLA-4 surface retention conditional on metabolism and vitamin D(3), including genetic variants in interleukin-7 receptor-α (IL7RA*C), interleukin-2 receptor-α (IL2RA*T), MGAT1 (IV(A)V(T-T)) and CTLA-4 (Thr17Ala). Downregulation of Mgat1 by IL7RA*C and IL2RA*T is opposed by MGAT1 (IV(A)V(T-T)) and vitamin D(3), optimizing branching and mitigating MS risk when combined with enhanced CTLA-4 N-glycosylation by CTLA-4 Thr17. Our data suggest a molecular mechanism in MS whereby multiple environmental and genetic inputs lead to dysregulation of a final common pathway, namely N-glycosylation.
0 Communities
1 Members
0 Resources
22 MeSH Terms
Genetic variants associated with breast-cancer risk: comprehensive research synopsis, meta-analysis, and epidemiological evidence.
Zhang B, Beeghly-Fadiel A, Long J, Zheng W
(2011) Lancet Oncol 12: 477-88
MeSH Terms: Antigens, CD, Aromatase, Ataxia Telangiectasia Mutated Proteins, Breast Neoplasms, CTLA-4 Antigen, Caspase 8, Cell Cycle Proteins, Checkpoint Kinase 2, DNA-Binding Proteins, Evidence-Based Medicine, Female, Genetic Predisposition to Disease, Humans, Mutation, Nuclear Proteins, Protein-Serine-Threonine Kinases, Risk Assessment, Risk Factors, Telomerase, Tumor Suppressor Protein p53, Tumor Suppressor Proteins
Show Abstract · Added December 10, 2013
BACKGROUND - More than 1000 reports have been published in the past two decades on associations between variants in candidate genes and risk of breast cancer. Results have been generally inconsistent. We did a literature search and meta-analyses to provide a synopsis of the current understanding of the genetic architecture of breast-cancer risk.
METHODS - A systematic literature search for candidate-gene association studies of breast-cancer risk was done in two stages, using PubMed on or before Feb 28, 2010. A total of 24,500 publications were identified, of which 1059 were deemed eligible for inclusion. Meta-analyses were done for 279 genetic variants in 128 candidate genes or chromosomal loci that had at least three data sources. Variants with significant associations by meta-analysis were assessed using the Venice criteria and scored as having strong, moderate, or weak cumulative evidence for an association with breast-cancer risk.
FINDINGS - 51 variants in 40 genes showed significant associations with breast-cancer risk. Cumulative epidemiological evidence of an association was graded as strong for ten variants in six genes (ATM, CASP8, CHEK2, CTLA4, NBN, and TP53), moderate for four variants in four genes (ATM, CYP19A1, TERT, and XRCC3), and weak for 37 variants. Additionally, in meta-analyses that included a minimum of 10,000 cases and 10,000 controls, convincing evidence of no association with breast-cancer risk was identified for 45 variants in 37 genes.
INTERPRETATION - Whereas most genetic variants assessed in previous candidate-gene studies showed no association with breast-cancer risk in meta-analyses, 14 variants in nine genes had moderate to strong evidence for an association. Further evaluation of these variants is warranted.
FUNDING - US National Cancer Institute.
Copyright © 2011 Elsevier Ltd. All rights reserved.
0 Communities
3 Members
0 Resources
21 MeSH Terms
Improved survival with ipilimumab in patients with metastatic melanoma.
Hodi FS, O'Day SJ, McDermott DF, Weber RW, Sosman JA, Haanen JB, Gonzalez R, Robert C, Schadendorf D, Hassel JC, Akerley W, van den Eertwegh AJ, Lutzky J, Lorigan P, Vaubel JM, Linette GP, Hogg D, Ottensmeier CH, Lebbé C, Peschel C, Quirt I, Clark JI, Wolchok JD, Weber JS, Tian J, Yellin MJ, Nichol GM, Hoos A, Urba WJ
(2010) N Engl J Med 363: 711-23
MeSH Terms: Antibodies, Monoclonal, Antigens, CD, CTLA-4 Antigen, Cancer Vaccines, Combined Modality Therapy, Double-Blind Method, Female, Humans, Ipilimumab, Kaplan-Meier Estimate, Male, Melanoma, Middle Aged, Skin Neoplasms, Treatment Outcome
Show Abstract · Added March 20, 2014
BACKGROUND - An improvement in overall survival among patients with metastatic melanoma has been an elusive goal. In this phase 3 study, ipilimumab--which blocks cytotoxic T-lymphocyte-associated antigen 4 to potentiate an antitumor T-cell response--administered with or without a glycoprotein 100 (gp100) peptide vaccine was compared with gp100 alone in patients with previously treated metastatic melanoma.
METHODS - A total of 676 HLA-A*0201-positive patients with unresectable stage III or IV melanoma, whose disease had progressed while they were receiving therapy for metastatic disease, were randomly assigned, in a 3:1:1 ratio, to receive ipilimumab plus gp100 (403 patients), ipilimumab alone (137), or gp100 alone (136). Ipilimumab, at a dose of 3 mg per kilogram of body weight, was administered with or without gp100 every 3 weeks for up to four treatments (induction). Eligible patients could receive reinduction therapy. The primary end point was overall survival.
RESULTS - The median overall survival was 10.0 months among patients receiving ipilimumab plus gp100, as compared with 6.4 months among patients receiving gp100 alone (hazard ratio for death, 0.68; P<0.001). The median overall survival with ipilimumab alone was 10.1 months (hazard ratio for death in the comparison with gp100 alone, 0.66; P=0.003). No difference in overall survival was detected between the ipilimumab groups (hazard ratio with ipilimumab plus gp100, 1.04; P=0.76). Grade 3 or 4 immune-related adverse events occurred in 10 to 15% of patients treated with ipilimumab and in 3% treated with gp100 alone. There were 14 deaths related to the study drugs (2.1%), and 7 were associated with immune-related adverse events.
CONCLUSIONS - Ipilimumab, with or without a gp100 peptide vaccine, as compared with gp100 alone, improved overall survival in patients with previously treated metastatic melanoma. Adverse events can be severe, long-lasting, or both, but most are reversible with appropriate treatment. (Funded by Medarex and Bristol-Myers Squibb; ClinicalTrials.gov number, NCT00094653.)
0 Communities
1 Members
0 Resources
15 MeSH Terms
A critical role for protein kinase C-theta-mediated T cell survival in cardiac allograft rejection.
Manicassamy S, Yin D, Zhang Z, Molinero LL, Alegre ML, Sun Z
(2008) J Immunol 181: 513-20
MeSH Terms: Animals, Antibodies, Monoclonal, Antigens, CD, CD40 Ligand, CTLA-4 Antigen, Cell Survival, Cells, Cultured, Female, Graft Rejection, Heart Transplantation, Homeodomain Proteins, Immunoglobulins, Isoenzymes, Lymphocyte Culture Test, Mixed, Mice, Mice, Knockout, Protein Kinase C, Protein Kinase C-theta, T-Lymphocytes, Transplantation, Homologous, bcl-X Protein
Show Abstract · Added December 10, 2013
Protein kinase C (PKC)-theta mediates the critical TCR signals required for T cell activation. Previously, we have shown that in response to TCR stimulation, PKC-theta-/- T cells undergo apoptosis due to greatly reduced levels of the anti-apoptotic molecule, Bcl-xL. In this study, we demonstrate that PKC-theta-regulated expression of Bcl-xL is essential for T cell-mediated cardiac allograft rejection. Rag1-/- mice reconstituted with wild-type T cells readily rejected fully mismatched cardiac allografts, whereas Rag1-/- mice reconstituted with PKC-theta-/- T cells failed to promote rejection. Transgenic expression of Bcl-xL in PKC-theta-/- T cells was sufficient to restore cardiac allograft rejection, suggesting that PKC-theta-regulated survival is required for T cell-mediated cardiac allograft rejection in this adoptive transfer model. In contrast to adoptive transfer experiments, intact PKC-theta-/- mice displayed delayed, but successful cardiac allograft rejection, suggesting the potential compensation for PKC-theta function. Finally, a subtherapeutic dose of anti-CD154 Ab or CTLA4-Ig, which was not sufficient to prevent cardiac allograft rejection in the wild-type mice, prevented heart rejection in the PKC-theta-/- mice. Thus, in combination with other treatments, inhibition of PKC-theta may facilitate achieving long-term survival of allografts.
0 Communities
1 Members
0 Resources
21 MeSH Terms
Complex N-glycan number and degree of branching cooperate to regulate cell proliferation and differentiation.
Lau KS, Partridge EA, Grigorian A, Silvescu CI, Reinhold VN, Demetriou M, Dennis JW
(2007) Cell 129: 123-34
MeSH Terms: Animals, Antigens, CD, Antigens, Differentiation, CTLA-4 Antigen, Cell Differentiation, Cell Line, Cell Line, Tumor, Cell Proliferation, Endocytosis, Glycoproteins, Glycosylation, Golgi Apparatus, Hexosamines, Humans, Kinetics, Mice, Mice, Transgenic, Models, Biological, Polysaccharides, Receptor Protein-Tyrosine Kinases, T-Lymphocytes, Uridine Diphosphate N-Acetylglucosamine
Show Abstract · Added November 15, 2013
The number of N-glycans (n) is a distinct feature of each glycoprotein sequence and cooperates with the physical properties of the Golgi N-glycan-branching pathway to regulate surface glycoprotein levels. The Golgi pathway is ultrasensitive to hexosamine flux for the production of tri- and tetra-antennary N-glycans, which bind to galectins and form a molecular lattice that opposes glycoprotein endocytosis. Glycoproteins with few N-glycans (e.g., TbetaR, CTLA-4, and GLUT4) exhibit enhanced cell-surface expression with switch-like responses to increasing hexosamine concentration, whereas glycoproteins with high numbers of N-glycans (e.g., EGFR, IGFR, FGFR, and PDGFR) exhibit hyperbolic responses. Computational and experimental data reveal that these features allow nutrient flux stimulated by growth-promoting high-n receptors to drive arrest/differentiation programs by increasing surface levels of low-n glycoproteins. We have identified a mechanism for metabolic regulation of cellular transition between growth and arrest in mammals arising from apparent coevolution of N-glycan number and branching.
0 Communities
1 Members
0 Resources
22 MeSH Terms
Promotion of allograft survival by CD4+CD25+ regulatory T cells: evidence for in vivo inhibition of effector cell proliferation.
Lee MK, Moore DJ, Jarrett BP, Lian MM, Deng S, Huang X, Markmann JW, Chiaccio M, Barker CF, Caton AJ, Markmann JF
(2004) J Immunol 172: 6539-44
MeSH Terms: Animals, Antigens, CD, Antigens, Differentiation, CD4 Antigens, CTLA-4 Antigen, Graft Rejection, Graft Survival, Interleukin-10, Lymphocyte Activation, Mice, Mice, Inbred BALB C, Receptors, Interleukin-2, Skin Transplantation, T-Lymphocyte Subsets, Transforming Growth Factor beta, Transplantation, Homologous
Show Abstract · Added October 24, 2013
Regulatory T cells preserve tolerance to peripheral self-Ags and may control the response to allogeneic tissues to promote transplantation tolerance. Although prior studies have demonstrated prolonged allograft survival in the presence of regulatory T cells (T-reg), data documenting the capacity of these cells to promote tolerance in immunocompetent transplant models are lacking, and the mechanism of suppression in vivo remains unclear. We used a TCR transgenic model of allograft rejection to characterize the in vivo activity of CD4(+)CD25(+) T-reg. We demonstrate that graft Ag-specific T-reg effectively intercede in the rejection response of naive T cells to established skin allografts. Furthermore, CFSE labeling demonstrates impaired proliferation of naive graft Ag-specific T cells in the draining lymph node in the presence of T-reg. These results confirm the efficacy of T-reg in promoting graft survival and suggest that their suppressive action is accomplished in part through inhibition of proliferation.
0 Communities
1 Members
0 Resources
16 MeSH Terms