scholarly journals Neoadjuvant PROSTVAC prior to radical prostatectomy enhances T-cell infiltration into the tumor immune microenvironment in men with prostate cancer

2020 ◽  
Vol 8 (1) ◽  
pp. e000655 ◽  
Author(s):  
Houssein Abdul Sater ◽  
Jennifer L Marté ◽  
Renee N Donahue ◽  
Beatriz Walter-Rodriguez ◽  
Christopher R Heery ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Immune Response ◽  
T Cell ◽  
Radical Prostatectomy ◽  
Mononuclear Cells ◽  
Intracellular Cytokine Staining ◽  
Specific Antigen ◽  
Cd8 T Cell ◽  
Cd4 T Cell ◽  
Cell Immunity

BackgroundClinical trials have shown the ability of therapeutic vaccines to generate immune responses to tumor-associated antigens (TAAs). What is relatively less known is if this translates into immune-cell (IC) infiltration into the tumor microenvironment. This study examined whether neoadjuvant prostate-specific antigen (PSA)-targeted vaccination with PROSTVAC could induce T-cell immunity, particularly at the tumor site.MethodsAn open-label, phase II study of neoadjuvant PROSTVAC vaccine enrolled 27 patients with localized prostate cancer awaiting radical prostatectomy (RP). We evaluated increases in CD4 and CD8 T-cell infiltrates (RP tissue vs baseline biopsies) using a six-color multiplex immunofluorescence Opal method. Antigen-specific responses were assessed by intracellular cytokine staining after in vitro stimulation of peripheral blood mononuclear cells with overlapping 15-mer peptide pools encoding the TAAs PSA, brachyury and MUC-1.ResultsOf 27 vaccinated patients, 26 had matched prevaccination (biopsy) and postvaccination (RP) prostate samples available for non-compartmentalized analysis (NCA) and compartmentalized analysis (CA). Tumor CD4 T-cell infiltrates were significantly increased in postvaccination RP specimens compared with baseline biopsies by NCA (median 176/mm² vs 152/mm²; IQR 136–317/mm² vs 69–284/mm²; p=0.0249; median ratio 1.20; IQR 0.64–2.25). By CA, an increase in both CD4 T-cell infiltrates at the tumor infiltrative margin (median 198/mm² vs 151/mm²; IQR 123–500/mm² vs 85–256/mm²; p=0.042; median ratio 1.44; IQR 0.59–4.17) and in CD8 T-cell infiltrates at the tumor core (median 140/mm² vs 105/mm²; IQR 91–175/mm² vs 83–163/mm²; p=0.036; median ratio 1.25; IQR 0.88–2.09) were noted in postvaccination RP specimens compared with baseline biopsies. A total of 13/25 patients (52%) developed peripheral T-cell responses to any of the three tested TAAs (non-neoantigens); five of these had responses to more than one antigen of the three evaluated.ConclusionNeoadjuvant PROSTVAC can induce both tumor immune response and peripheral immune response.Trial registration numberNCT02153918.

scholarly journals Safety and exceptional immunogenicity of novel 5T4 viral vectored vaccination regimes in early stage prostate cancer: a phase I clinical trial

2020 ◽  
Author(s):  
Federica Cappuccini ◽  
Richard Bryant ◽  
Emily Pollock ◽  
Lucy Carter ◽  
Clare Verrill ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
T Cells ◽  
T Cell ◽  
Mononuclear Cells ◽  
Ex Vivo ◽  
Early Stage ◽  
Specific Antigen ◽  
T Cell Responses ◽  
Cell Responses ◽  
Cell Immunity

AbstractProstate cancer (PCa) has been under investigation as a target for antigen-specific immunotherapies in metastatic disease settings for a decade. However, neither of the two clinically most developed prostate cancer vaccines, Sipuleucel-T and ProstVac, induce strong T cell immunity. In this first-in-man study, VANCE, we evaluated a novel vaccination platform based on two replication-deficient viruses, chimpanzee adenovirus (ChAd) and MVA (Modified Vaccinia Ankara), targeting the oncofetal self-antigen 5T4 in early stage PCa. Forty patients, either newly diagnosed with early stage prostate cancer and scheduled for radical prostatectomy or patients with stable disease on an active surveillance protocol, were recruited to the study to assess the vaccine safety and T cell immunogenicity. Secondary and exploratory endpoints included immune infiltration into the prostate, prostate specific antigen (PSA) change and assessment of phenotype and functionality of antigen-specific T cells. The vaccine had an excellent safety profile. Vaccination-induced 5T4-specific T cell responses were measured in blood by ex vivo IFN-γ ELISpot and were detected in the majority of patients with a mean level in responders of 198 spot-forming cells (SFC) per million peripheral blood mononuclear cells (PBMCs). Flow cytometry analysis demonstrated the presence of both CD8+ and CD4+ polyfunctional 5T4-specific T cells in the circulation. 5T4-reactive tumour infiltrating lymphocytes (TILs) were isolated from post-treatment prostate tissue. Some of the patients had a transient PSA rise 2-8 weeks following vaccination, possibly indicating an inflammatory response in the target organ. The potent T cell responses elicited support the evaluation of these vectored vaccine in efficacy trials.

Role of CD8 T-cell in immune response to tuberculosis-specific antigen in QuantiFERON-TB Gold Plus

2020 ◽  
Vol 26 (6) ◽  
pp. 570-574
Author(s):  
Mizue Tsuyuzaki ◽  
Hidetoshi Igari ◽  
Nao Okada ◽  
Kiminori Suzuki
Keyword(s):  
Immune Response ◽  
T Cell ◽  
Specific Antigen ◽  
Cd8 T Cell

scholarly journals Identification of immunogenic LY6K long peptide encompassing both CD4+and CD8+T-cell epitopes and eliciting CD4+T-cell immunity in patients with malignant disease

2014 ◽  
Vol 3 (3) ◽  
pp. e28100 ◽  
Author(s):  
Yusuke Tomita ◽  
Akira Yuno ◽  
Hirotake Tsukamoto ◽  
Satoru Senju ◽  
Yasuhiro Kuroda ◽  
...  
Keyword(s):  
T Cell ◽  
Malignant Disease ◽  
Cd8 T Cell ◽  
T Cell Immunity ◽  
Cd4 T Cell ◽  
T Cell Epitopes ◽  
Cell Immunity

scholarly journals Identification of CDCA1-derived long peptides bearing both CD4+and CD8+T-cell epitopes: CDCA1-specific CD4+T-cell immunity in cancer patients

2013 ◽  
Vol 134 (2) ◽  
pp. 352-366 ◽  
Author(s):  
Yusuke Tomita ◽  
Akira Yuno ◽  
Hirotake Tsukamoto ◽  
Satoru Senju ◽  
Sachiko Yoshimura ◽  
...  
Keyword(s):  
T Cell ◽  
Cancer Patients ◽  
Cd8 T Cell ◽  
T Cell Immunity ◽  
Cd4 T Cell ◽  
T Cell Epitopes ◽  
Cell Immunity

scholarly journals CD4+ T-cell help amplifies innate signals for primary CD8+ T-cell immunity

2016 ◽  
Vol 272 (1) ◽  
pp. 52-64 ◽  
Author(s):  
Sammy Bedoui ◽  
William R. Heath ◽  
Scott N. Mueller
Keyword(s):  
T Cell ◽  
Cd8 T Cell ◽  
T Cell Immunity ◽  
Cd4 T Cell ◽  
Cd4 T Cell Help ◽  
Cell Immunity ◽  
T Cell Help

scholarly journals Comprehensive Analysis of Cell Population Dynamics and Related Core Genes During Vitiligo Development

2021 ◽  
Vol 12 ◽  
Author(s):  
Jingzhan Zhang ◽  
Shirong Yu ◽  
Wen Hu ◽  
Man Wang ◽  
Dilinuer Abudoureyimu ◽  
...  
Keyword(s):  
Gene Expression ◽  
Immune Response ◽  
T Cells ◽  
T Cell ◽  
Peripheral Blood ◽  
Immune Cell ◽  
Cd8 T Cell ◽  
Cd4 T Cell ◽  
Healthy Controls ◽  
Cell Abundance

Vitiligo is a common immune-related depigmentation condition, and its pathogenesis remains unclear. This study used a combination of bioinformatics methods and expression analysis techniques to explore the relationship between immune cell infiltration and gene expression in vitiligo. Previously reported gene expression microarray data from the skin (GSE53146 and GSE75819) and peripheral blood (GSE80009 and GSE90880) of vitiligo patients and healthy controls was used in the analysis. R software was used to filter the differentially expressed genes (DEGs) in each dataset, and the KOBAS 2.0 server was used to perform functional enrichment analysis. Compared with healthy controls, the upregulated genes in skin lesions and peripheral blood leukocytes of vitiligo patents were highly enriched in immune response pathways and inflammatory response signaling pathways. Immunedeconv software and the EPIC method were used to analyze the expression levels of marker genes to obtain the immune cell population in the samples. In the lesional skin of vitiligo patients, the proportions of macrophages, B cells and NK cells were increased compared with healthy controls. In the peripheral blood of vitiligo patients, CD8+ T cells and macrophages were significantly increased. A coexpression analysis of the cell populations and DEGs showed that differentially expressed immune and inflammation response genes had a strong positive correlation with macrophages. The TLR4 receptor pathway, interferon gamma-mediated signaling pathway and lipopolysaccharide-related pathway were positively correlated with CD4+ T cells. Regarding immune response-related genes, the overexpression of IFITM2, TNFSF10, GZMA, ADAMDEC1, NCF2, ADAR, SIGLEC16, and WIPF2 were related to macrophage abundance, while the overexpression of ICOS, GPR183, RGS1, ILF2 and CD28 were related to CD4+ T cell abundance. GZMA and CXCL10 expression were associated with CD8+ T cell abundance. Regarding inflammatory response-related genes, the overexpression of CEBPB, ADAM8, CXCR3, and TNIP3 promoted macrophage infiltration. Only ADORA1 expression was associated with CD4+ T cell infiltration. ADAM8 and CXCL10 expression were associated with CD8+ T cell abundance. The overexpression of CCL18, CXCL10, FOS, NLRC4, LY96, HCK, MYD88, and KLRG1, which are related to inflammation and immune responses, were associated with macrophage abundance. We also found that immune cells infiltration in vitiligo was associated with antigen presentation-related genes expression. The genes and pathways identified in this study may point to new directions for vitiligo treatment.

Blocking the regulatory T cell molecule LAG-3 augments in vivo anti-tumor immunity in an autochthonous model of prostate cancer

2006 ◽  
Vol 24 (18_suppl) ◽  
pp. 2573-2573
Author(s):  
C. G. Drake ◽  
C. Kelleher ◽  
T. Bruno ◽  
T. Harris ◽  
D. Flies ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
T Cells ◽  
T Cell ◽  
Regulatory T Cell ◽  
Specific Antigen ◽  
Cell Activity ◽  
Cd8 T Cell ◽  
Regulatory Function

2573 Background: LAG-3 is a CD4 homolog expressed on activated T cells, NK cells, tumor infiltrating lymphocytes (TIL), and plasmacytoid dendritic cells. Recently, we showed that LAG-3 was relatively overexpressed in specific T cells rendered unresponsive in vivo by the presence of cognate self-antigen. These anergic T cells display regulatory function both in vitro and in vivo, and blockade of LAG-3 with a non-depleting monoclonal antibody significantly mitigates their regulatory T cell activity. Methods: Using a novel model of prostate cancer in which a tumor-specific antigen is expressed in autochthonous tumors, we tested whether treatment with a non-depleting anti-LAG-3 antibody affected trafficking and function of tumor-specific T cells. Results: LAG-3 blockade significantly augments specific CD8 T cell trafficking to antigen-expressing tumors, but not to normal tissue. Most significantly, LAG-3 blockade functionally reversed CD8 T cell tolerance as assayed by an in vivo cytotoxic T lymphocyte (CTL) assay. Combining LAG-3 blockade with specific anti-tumor vaccination results in a dramatic increase in activated CD8 T cells in the tumor parenchyma. Conclusions: Taken together, these data support the concept that treatment with a LAG-3 blocking antibody may significantly delay disease progression in patients with cancer. We have recently generated a panel of monoclonal antibodies directed against human LAG-3; several of these antibodies significantly augment human T cell responses in vitro. No significant financial relationships to disclose.

scholarly journals Identification of Promiscuous KIF20A Long Peptides Bearing Both CD4+ and CD8+ T-cell Epitopes: KIF20A-Specific CD4+ T-cell Immunity in Patients with Malignant Tumor

2013 ◽  
Vol 19 (16) ◽  
pp. 4508-4520 ◽  
Author(s):  
Yusuke Tomita ◽  
Akira Yuno ◽  
Hirotake Tsukamoto ◽  
Satoru Senju ◽  
Yasuhiro Kuroda ◽  
...  
Keyword(s):  
T Cell ◽  
Malignant Tumor ◽  
Cd8 T Cell ◽  
T Cell Immunity ◽  
Cd4 T Cell ◽  
T Cell Epitopes ◽  
Cell Immunity

scholarly journals Effect of Lactobacillus plantarum IS-10506 on blood lipopolysaccharide level and immune response in HIV-infected children

2019 ◽  
Author(s):  
Alpha Fardah Athiyyah ◽  
Herwina Brahmantya ◽  
Stephani Dwiastuti ◽  
Andy Darma ◽  
Dwiyanti Puspitasari ◽  
...  
Keyword(s):  
Immune Response ◽  
T Cell ◽  
Cell Count ◽  
Lactobacillus Plantarum ◽  
Cd8 T Cell ◽  
Cd4 T Cell ◽  
Controlled Study ◽  
Probiotic Group ◽  
Cell Ratio ◽  
Cd4 T Cell Count

Background and Objectives: HIV enteropathy may cause disruption of the intestinal barrier, leading to a loss of CD4+ T cells, increased intestinal permeability, and microbial translocation. Lactobacillus plantarum IS-10506 has the ability to improve gut barrier function. This study investigated the effect of L. plantarum IS-10506 on a number of biomarkers of en- teropathy-related damage in HIV-infected paediatric patients undergoing antiretroviral therapy (ARV). Materials and Methods: A randomized, double-blind, placebo-controlled study was conducted on 2-18 year-old children, diagnosed as HIV infected according to the WHO 2007 criteria who had received ARV for ≥ 6 months. Subjects were exclud- ed if ARV therapy was discontinued or the patients took probiotics ≥ 2 weeks prior to the study or during the study period. Subjects were randomized into a probiotic group and placebo group. The probiotic group received L. plantarum IS-10506 2.86 × 1010  cfu/day for 6 days. Blood lipopolysaccharide (LPS) level, serum CD4+ T cell count, serum CD8+ T cell count, CD4+/CD8+ T cell ratio, and faecal sIgA level were assessed as biomarkers. Results: Twenty-one subjects completed this study. The blood LPS level decreased significantly in the probiotic group (p = 0.001). There was no significant difference in absolute CD4+ T cell count, percent CD4+ cells, absolute CD8+ T cell count, CD4+/CD8+ T cell ratio, or faecal sIgA. No serious adverse events were reported. Conclusion: The probiotic L. plantarum IS-10506 reduced the blood LPS level but showed no effect on the humoral mucosa and systemic immune response in HIV-infected children undergoing ARV therapy.

Sign in / Sign up

Export Citation Format

Share Document