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  • 96
    Addgene inc fugw gfp
    KEY RESOURCES TABLE
    Fugw Gfp, supplied by Addgene inc, used in various techniques. Bioz Stars score: 96/100, based on 1 PubMed citations. ZERO BIAS - scores, article reviews, protocol conditions and more
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    86
    Illumina Inc porcine snp60k bead chip
    (a) Overview of study design. Genotyping arrays: Illumina Porcine <t>SNP60K</t> Bead Chip (N = 10,870), the GeneSeek Genomic Profiler (GGP) Porcine SNP80 BeadChip (N = 4,724), the GGP Procine SNP50 BeadChip (N = 29,789), the KPS Porcine Breeding Chip (N = 21,618), the GenoBaits Porcine SNP50K BeadChip (N = 454) and low-coverage sequence (N = 2,873). WGS: Whole genome sequence. GWAS: genome-wide association study. TWAS: transcriptome-wide association study. SMR: summary data-based Mendelian randomization. (b-c) Principal component analysis of PGRP (b) and GWAS (c) populations, which were conducted based on all 57,600 individuals (samples with genotype data) and a total of 1,603 shared array SNPs using PLINK (v1.90) (parameters: --geno 0.1 --mind 0.1 --indep-pairwise 50 5 0.5 --maf 0.01 and --pca 10). The first two principal components were plotted using the geom_point function from ggplot2 (v3.3.6) in R (v4.1.2). (d) The imputation accuracy of PGRP in independent WGS data. This was 93.34% ± 7.64% for Duroc pigs (commercial breed and within PGRP) and 91.13% ± 10.49% for Suhuai pigs (domesticated breed and outside PGRP). The imputation accuracy was calculated as the concordance rate between the imputed and observed genotypes. (e) The total sample size for each trait in meta-GWAS analyses. Traits were classified into five main categories.
    Porcine Snp60k Bead Chip, supplied by Illumina Inc, used in various techniques. Bioz Stars score: 86/100, based on 1 PubMed citations. ZERO BIAS - scores, article reviews, protocol conditions and more
    https://www.bioz.com/result/porcine snp60k bead chip/product/Illumina Inc
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    Dow Chemical mixed amphetamine salts loaded beads 500 grams ethyl cellulose
    (a) Overview of study design. Genotyping arrays: Illumina Porcine <t>SNP60K</t> Bead Chip (N = 10,870), the GeneSeek Genomic Profiler (GGP) Porcine SNP80 BeadChip (N = 4,724), the GGP Procine SNP50 BeadChip (N = 29,789), the KPS Porcine Breeding Chip (N = 21,618), the GenoBaits Porcine SNP50K BeadChip (N = 454) and low-coverage sequence (N = 2,873). WGS: Whole genome sequence. GWAS: genome-wide association study. TWAS: transcriptome-wide association study. SMR: summary data-based Mendelian randomization. (b-c) Principal component analysis of PGRP (b) and GWAS (c) populations, which were conducted based on all 57,600 individuals (samples with genotype data) and a total of 1,603 shared array SNPs using PLINK (v1.90) (parameters: --geno 0.1 --mind 0.1 --indep-pairwise 50 5 0.5 --maf 0.01 and --pca 10). The first two principal components were plotted using the geom_point function from ggplot2 (v3.3.6) in R (v4.1.2). (d) The imputation accuracy of PGRP in independent WGS data. This was 93.34% ± 7.64% for Duroc pigs (commercial breed and within PGRP) and 91.13% ± 10.49% for Suhuai pigs (domesticated breed and outside PGRP). The imputation accuracy was calculated as the concordance rate between the imputed and observed genotypes. (e) The total sample size for each trait in meta-GWAS analyses. Traits were classified into five main categories.
    Mixed Amphetamine Salts Loaded Beads 500 Grams Ethyl Cellulose, supplied by Dow Chemical, used in various techniques. Bioz Stars score: 86/100, based on 1 PubMed citations. ZERO BIAS - scores, article reviews, protocol conditions and more
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    Miltenyi Biotec cd8 microbeads
    Compared to other costimulatory receptors, 4‐1BB is more prominently expressed on <t>CD8</t> + TILs, especially on PD‐1 high cells. (A) The percentage of CD8 + TILs that expressed various activation‐induced costimulatory receptors belonging to the TNFRSF. Left panel shows representative flow cytometry histograms. (B) Percentages of 4‐1BB pos CD8 + TILs in various cancer types: OV, ovarian cancer; NSCLC, non‐small‐cell lung cancer; ICC, intrahepatic cholangiocellular carcinoma; CRC, colorectal cancer; and GBM, glioblastoma multiforme. (C) 4‐1BB expression pattern across different CD8 + T‐cell fractions. The percentage of 4‐1BB pos cells was compared among the different T‐cell fractions of total and NY‐ESO‐1 157‐165 –specific CD8 + T cells. Left panel shows representative flow cytometry plots. (D) 4‐1BB expression according to differential PD‐1 expression levels. The percentage of 4‐1BB pos cells was compared among PD‐1 high , PD‐1 int and PD‐1 neg subpopulations of total and NY‐ESO‐1 157‐165 –specific CD8 + TILs. (E) Correlations between the percentage of 4‐1BB pos CD8 + TILs and PD‐1 high CD8 + TILs among the total CD8 + TILs and NY‐ESO‐1 157 –specific CD8 + TILs. Upper panel shows representative flow cytometry plots. Data are presented as mean ± SEM. * P < 0.05; ** P < 0.01; *** P < 0.001. Abbreviation: ns, not significant.
    Cd8 Microbeads, supplied by Miltenyi Biotec, used in various techniques. Bioz Stars score: 86/100, based on 1 PubMed citations. ZERO BIAS - scores, article reviews, protocol conditions and more
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    Dow Chemical mixed amphetamine salts loaded beads masl 500 grams ethyl cellulose
    Compared to other costimulatory receptors, 4‐1BB is more prominently expressed on <t>CD8</t> + TILs, especially on PD‐1 high cells. (A) The percentage of CD8 + TILs that expressed various activation‐induced costimulatory receptors belonging to the TNFRSF. Left panel shows representative flow cytometry histograms. (B) Percentages of 4‐1BB pos CD8 + TILs in various cancer types: OV, ovarian cancer; NSCLC, non‐small‐cell lung cancer; ICC, intrahepatic cholangiocellular carcinoma; CRC, colorectal cancer; and GBM, glioblastoma multiforme. (C) 4‐1BB expression pattern across different CD8 + T‐cell fractions. The percentage of 4‐1BB pos cells was compared among the different T‐cell fractions of total and NY‐ESO‐1 157‐165 –specific CD8 + T cells. Left panel shows representative flow cytometry plots. (D) 4‐1BB expression according to differential PD‐1 expression levels. The percentage of 4‐1BB pos cells was compared among PD‐1 high , PD‐1 int and PD‐1 neg subpopulations of total and NY‐ESO‐1 157‐165 –specific CD8 + TILs. (E) Correlations between the percentage of 4‐1BB pos CD8 + TILs and PD‐1 high CD8 + TILs among the total CD8 + TILs and NY‐ESO‐1 157 –specific CD8 + TILs. Upper panel shows representative flow cytometry plots. Data are presented as mean ± SEM. * P < 0.05; ** P < 0.01; *** P < 0.001. Abbreviation: ns, not significant.
    Mixed Amphetamine Salts Loaded Beads Masl 500 Grams Ethyl Cellulose, supplied by Dow Chemical, used in various techniques. Bioz Stars score: 86/100, based on 1 PubMed citations. ZERO BIAS - scores, article reviews, protocol conditions and more
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    Image Search Results


    KEY RESOURCES TABLE

    Journal: Cell

    Article Title: Genome-nuclear lamina interactions regulate cardiac stem cell lineage restriction

    doi: 10.1016/j.cell.2017.09.018

    Figure Lengend Snippet: KEY RESOURCES TABLE

    Article Snippet: FUGW-GFP , Addgene , Cat# 14883.

    Techniques: Recombinant, Blocking Assay, Magnetic Beads, Nick Translation, Expressing, shRNA, Software, Imaging

    (a) Overview of study design. Genotyping arrays: Illumina Porcine SNP60K Bead Chip (N = 10,870), the GeneSeek Genomic Profiler (GGP) Porcine SNP80 BeadChip (N = 4,724), the GGP Procine SNP50 BeadChip (N = 29,789), the KPS Porcine Breeding Chip (N = 21,618), the GenoBaits Porcine SNP50K BeadChip (N = 454) and low-coverage sequence (N = 2,873). WGS: Whole genome sequence. GWAS: genome-wide association study. TWAS: transcriptome-wide association study. SMR: summary data-based Mendelian randomization. (b-c) Principal component analysis of PGRP (b) and GWAS (c) populations, which were conducted based on all 57,600 individuals (samples with genotype data) and a total of 1,603 shared array SNPs using PLINK (v1.90) (parameters: --geno 0.1 --mind 0.1 --indep-pairwise 50 5 0.5 --maf 0.01 and --pca 10). The first two principal components were plotted using the geom_point function from ggplot2 (v3.3.6) in R (v4.1.2). (d) The imputation accuracy of PGRP in independent WGS data. This was 93.34% ± 7.64% for Duroc pigs (commercial breed and within PGRP) and 91.13% ± 10.49% for Suhuai pigs (domesticated breed and outside PGRP). The imputation accuracy was calculated as the concordance rate between the imputed and observed genotypes. (e) The total sample size for each trait in meta-GWAS analyses. Traits were classified into five main categories.

    Journal: bioRxiv

    Article Title: Integrating large-scale meta-GWAS and PigGTEx resources to decipher the genetic basis of complex traits in pig

    doi: 10.1101/2023.10.09.561393

    Figure Lengend Snippet: (a) Overview of study design. Genotyping arrays: Illumina Porcine SNP60K Bead Chip (N = 10,870), the GeneSeek Genomic Profiler (GGP) Porcine SNP80 BeadChip (N = 4,724), the GGP Procine SNP50 BeadChip (N = 29,789), the KPS Porcine Breeding Chip (N = 21,618), the GenoBaits Porcine SNP50K BeadChip (N = 454) and low-coverage sequence (N = 2,873). WGS: Whole genome sequence. GWAS: genome-wide association study. TWAS: transcriptome-wide association study. SMR: summary data-based Mendelian randomization. (b-c) Principal component analysis of PGRP (b) and GWAS (c) populations, which were conducted based on all 57,600 individuals (samples with genotype data) and a total of 1,603 shared array SNPs using PLINK (v1.90) (parameters: --geno 0.1 --mind 0.1 --indep-pairwise 50 5 0.5 --maf 0.01 and --pca 10). The first two principal components were plotted using the geom_point function from ggplot2 (v3.3.6) in R (v4.1.2). (d) The imputation accuracy of PGRP in independent WGS data. This was 93.34% ± 7.64% for Duroc pigs (commercial breed and within PGRP) and 91.13% ± 10.49% for Suhuai pigs (domesticated breed and outside PGRP). The imputation accuracy was calculated as the concordance rate between the imputed and observed genotypes. (e) The total sample size for each trait in meta-GWAS analyses. Traits were classified into five main categories.

    Article Snippet: We genotyped these pigs from these 59 populations using low-coverage sequence (N = 2,873) or genotyping arrays, including the Illumina Porcine SNP60K Bead Chip (N = 10,870), the GeneSeek Genomic Profiler (GGP) Porcine SNP80 BeadChip (N = 4,724), the GGP Procine SNP50 BeadChip (N = 29,789), the KPS Porcine Breeding Chip (N = 21,618), the GenoBaits Porcine SNP50K BeadChip (N = 454).

    Techniques: Sequencing, GWAS

    Compared to other costimulatory receptors, 4‐1BB is more prominently expressed on CD8 + TILs, especially on PD‐1 high cells. (A) The percentage of CD8 + TILs that expressed various activation‐induced costimulatory receptors belonging to the TNFRSF. Left panel shows representative flow cytometry histograms. (B) Percentages of 4‐1BB pos CD8 + TILs in various cancer types: OV, ovarian cancer; NSCLC, non‐small‐cell lung cancer; ICC, intrahepatic cholangiocellular carcinoma; CRC, colorectal cancer; and GBM, glioblastoma multiforme. (C) 4‐1BB expression pattern across different CD8 + T‐cell fractions. The percentage of 4‐1BB pos cells was compared among the different T‐cell fractions of total and NY‐ESO‐1 157‐165 –specific CD8 + T cells. Left panel shows representative flow cytometry plots. (D) 4‐1BB expression according to differential PD‐1 expression levels. The percentage of 4‐1BB pos cells was compared among PD‐1 high , PD‐1 int and PD‐1 neg subpopulations of total and NY‐ESO‐1 157‐165 –specific CD8 + TILs. (E) Correlations between the percentage of 4‐1BB pos CD8 + TILs and PD‐1 high CD8 + TILs among the total CD8 + TILs and NY‐ESO‐1 157 –specific CD8 + TILs. Upper panel shows representative flow cytometry plots. Data are presented as mean ± SEM. * P < 0.05; ** P < 0.01; *** P < 0.001. Abbreviation: ns, not significant.

    Journal: Hepatology (Baltimore, Md.)

    Article Title: 4‐1BB Delineates Distinct Activation Status of Exhausted Tumor‐Infiltrating CD8 + T Cells in Hepatocellular Carcinoma

    doi: 10.1002/hep.30881

    Figure Lengend Snippet: Compared to other costimulatory receptors, 4‐1BB is more prominently expressed on CD8 + TILs, especially on PD‐1 high cells. (A) The percentage of CD8 + TILs that expressed various activation‐induced costimulatory receptors belonging to the TNFRSF. Left panel shows representative flow cytometry histograms. (B) Percentages of 4‐1BB pos CD8 + TILs in various cancer types: OV, ovarian cancer; NSCLC, non‐small‐cell lung cancer; ICC, intrahepatic cholangiocellular carcinoma; CRC, colorectal cancer; and GBM, glioblastoma multiforme. (C) 4‐1BB expression pattern across different CD8 + T‐cell fractions. The percentage of 4‐1BB pos cells was compared among the different T‐cell fractions of total and NY‐ESO‐1 157‐165 –specific CD8 + T cells. Left panel shows representative flow cytometry plots. (D) 4‐1BB expression according to differential PD‐1 expression levels. The percentage of 4‐1BB pos cells was compared among PD‐1 high , PD‐1 int and PD‐1 neg subpopulations of total and NY‐ESO‐1 157‐165 –specific CD8 + TILs. (E) Correlations between the percentage of 4‐1BB pos CD8 + TILs and PD‐1 high CD8 + TILs among the total CD8 + TILs and NY‐ESO‐1 157 –specific CD8 + TILs. Upper panel shows representative flow cytometry plots. Data are presented as mean ± SEM. * P < 0.05; ** P < 0.01; *** P < 0.001. Abbreviation: ns, not significant.

    Article Snippet: RNA‐sequencing (RNA‐seq) was performed on PD‐1 int , 4‐1BB neg PD‐1 high , and 4‐1BB pos PD‐1 high CD8 + TILs (n = 5) that were sorted using a FACS Aria II cell sorter (BD Biosciences), as well as on total CD8 + TILs sorted using CD8 Microbeads (n = 10; Miltenyi Biotec).

    Techniques: Activation Assay, Flow Cytometry, Expressing

    4‐1BB–expressing PD‐1 high CD8 + TILs feature immunophenotypically and transcriptionally prominent T‐cell activation. (A) Representative flow cytometry plot showing subpopulations of PD‐1 + CD8 + TILs according to differential expression of PD‐1 and 4‐1BB. (B,C) Percentages of CD39 + CD103 + cells (B) and CD38 + HLA‐DR + cells (C) among the PD‐1 int , 4‐1BB neg PD‐1 high , and 4‐1BB pos PD‐1 high subpopulations of total and NY‐ESO‐1 157 –specific CD8 + TILs. Left panels show representative flow cytometry plots (B,C). (D,E) RNA‐seq data comparing expression of genes related to T‐cell activation among FACS‐sorted PD‐1 int , 4‐1BB neg PD‐1 high and 4‐1BB pos PD‐1 high CD8 + TILs. (D) Heatmap showing expression levels of T‐cell activation gene signatures among the PD‐1 int , 4‐1BB neg PD‐1 high , and 4‐1BB pos PD‐1 high subpopulations. (E) Relative enrichment of T‐cell activation gene signatures among PD‐1 int , 4‐1BB neg PD‐1 high , and 4‐1BB pos PD‐1 high CD8 + TILs. Dashed line marks the significance threshold ( P = 0.05). * P < 0.05; *** P < 0.001.

    Journal: Hepatology (Baltimore, Md.)

    Article Title: 4‐1BB Delineates Distinct Activation Status of Exhausted Tumor‐Infiltrating CD8 + T Cells in Hepatocellular Carcinoma

    doi: 10.1002/hep.30881

    Figure Lengend Snippet: 4‐1BB–expressing PD‐1 high CD8 + TILs feature immunophenotypically and transcriptionally prominent T‐cell activation. (A) Representative flow cytometry plot showing subpopulations of PD‐1 + CD8 + TILs according to differential expression of PD‐1 and 4‐1BB. (B,C) Percentages of CD39 + CD103 + cells (B) and CD38 + HLA‐DR + cells (C) among the PD‐1 int , 4‐1BB neg PD‐1 high , and 4‐1BB pos PD‐1 high subpopulations of total and NY‐ESO‐1 157 –specific CD8 + TILs. Left panels show representative flow cytometry plots (B,C). (D,E) RNA‐seq data comparing expression of genes related to T‐cell activation among FACS‐sorted PD‐1 int , 4‐1BB neg PD‐1 high and 4‐1BB pos PD‐1 high CD8 + TILs. (D) Heatmap showing expression levels of T‐cell activation gene signatures among the PD‐1 int , 4‐1BB neg PD‐1 high , and 4‐1BB pos PD‐1 high subpopulations. (E) Relative enrichment of T‐cell activation gene signatures among PD‐1 int , 4‐1BB neg PD‐1 high , and 4‐1BB pos PD‐1 high CD8 + TILs. Dashed line marks the significance threshold ( P = 0.05). * P < 0.05; *** P < 0.001.

    Article Snippet: RNA‐sequencing (RNA‐seq) was performed on PD‐1 int , 4‐1BB neg PD‐1 high , and 4‐1BB pos PD‐1 high CD8 + TILs (n = 5) that were sorted using a FACS Aria II cell sorter (BD Biosciences), as well as on total CD8 + TILs sorted using CD8 Microbeads (n = 10; Miltenyi Biotec).

    Techniques: Expressing, Activation Assay, Flow Cytometry, RNA Sequencing Assay

    The percentage of 4‐1BB pos CD8 + TILs is positively correlated with the degree of overall activation of CD8 + TILs. (A) Correlations between the percentage of 4‐1BB pos CD8 + TILs and the percentages of CD39 + CD103 + cells and CD38 + HLA‐DR + cells, among total CD8 + TILs (left panel) and NY‐ESO‐1 157‐165 –specific CD8 + TILs (right panel). (B) RNA‐seq data from sorted total CD8 + TILs, analyzing the expression levels of T‐cell activation gene signatures, represented as the enrichment score obtained by GSVA. Correlations between the percentage of 4‐1BB pos CD8 + TILs and enrichment scores of T‐cell activation gene signatures were subsequently analyzed.

    Journal: Hepatology (Baltimore, Md.)

    Article Title: 4‐1BB Delineates Distinct Activation Status of Exhausted Tumor‐Infiltrating CD8 + T Cells in Hepatocellular Carcinoma

    doi: 10.1002/hep.30881

    Figure Lengend Snippet: The percentage of 4‐1BB pos CD8 + TILs is positively correlated with the degree of overall activation of CD8 + TILs. (A) Correlations between the percentage of 4‐1BB pos CD8 + TILs and the percentages of CD39 + CD103 + cells and CD38 + HLA‐DR + cells, among total CD8 + TILs (left panel) and NY‐ESO‐1 157‐165 –specific CD8 + TILs (right panel). (B) RNA‐seq data from sorted total CD8 + TILs, analyzing the expression levels of T‐cell activation gene signatures, represented as the enrichment score obtained by GSVA. Correlations between the percentage of 4‐1BB pos CD8 + TILs and enrichment scores of T‐cell activation gene signatures were subsequently analyzed.

    Article Snippet: RNA‐sequencing (RNA‐seq) was performed on PD‐1 int , 4‐1BB neg PD‐1 high , and 4‐1BB pos PD‐1 high CD8 + TILs (n = 5) that were sorted using a FACS Aria II cell sorter (BD Biosciences), as well as on total CD8 + TILs sorted using CD8 Microbeads (n = 10; Miltenyi Biotec).

    Techniques: Activation Assay, RNA Sequencing Assay, Expressing

    4‐1BB pos PD‐1 high CD8 + TILs exhibited higher levels of markers indicating T‐cell proliferation and reinvigoration compared to 4‐1BB neg PD‐1 high CD8 + TILs. (A) Heatmap showing expression levels of 569 DEGs between 4‐1BB neg PD‐1 high and 4‐1BB pos PD‐1 high CD8 + TILs. (B) Gene Ontology analysis for the DEGs that were up‐regulated in 4‐1BB pos PD‐1 high CD8 + TILs compared to in 4‐1BB neg PD‐1 high CD8 + TILs. (C) Percentage of Ki‐67 + cells compared between 4‐1BB pos PD‐1 high and 4‐1BB neg PD‐1 high CD8 + TILs. Left panel shows representative flow cytometry plot. (D) Kaplan‐Meier curve comparing survival outcomes among subgroups (i.e., high and low 4‐1BB signature groups) of HCC patients in the TCGA cohort, according to expression of the 4‐1BB signature. Cutoff was determined by the maximal chi‐square method. (E) GSEA was performed to compare the enrichment of a T‐cell–inflamed gene signature between the high and low 4‐1BB signature groups. (F) Expression levels of parameters involved in T‐cell reinvigoration (i.e., TCF‐1, CD28, and T‐bet/Eomes) were compared between 4‐1BB pos PD‐1 high and 4‐1BB neg PD‐1 high CD8 + TILs. Left panel shows representative flow cytometry plots. * P < 0.05; *** P < 0.001. Abbreviations: ACKR4, atypical chemokine receptor 4; CEACAM1, carcinoembryonic antigen‐related cell adhesion molecule 1; CLEC1B, C‐type lectin domain family 1 member B; CMTM2, CKLF‐like MARVEL transmembrane domain‐containing 2; CXCL5, C‐X‐C motif chemokine ligand 5; Eomes, eomesodermin; GO, Gene Ontology; GZMA, granzyme 1, cytotoxic T‐lymphocyte–associated serine esterase 3; GZMK, granzyme K (serine protease, granzyme 3; tryptase II); IL2RA, interleukin‐2 receptor agonist; KLRB1, killer cell lectin‐like receptor B1; Max, maximum; ncRNA, noncoding RNA; NES, normalized enrichment score; NLRP13, NOD‐like receptor family pyrin domain containing 13; T‐bet, T‐box–containing protein expressed in T cells; TGFBR1, transforming growth factor beta receptor 1; tRNA, total RNA.

    Journal: Hepatology (Baltimore, Md.)

    Article Title: 4‐1BB Delineates Distinct Activation Status of Exhausted Tumor‐Infiltrating CD8 + T Cells in Hepatocellular Carcinoma

    doi: 10.1002/hep.30881

    Figure Lengend Snippet: 4‐1BB pos PD‐1 high CD8 + TILs exhibited higher levels of markers indicating T‐cell proliferation and reinvigoration compared to 4‐1BB neg PD‐1 high CD8 + TILs. (A) Heatmap showing expression levels of 569 DEGs between 4‐1BB neg PD‐1 high and 4‐1BB pos PD‐1 high CD8 + TILs. (B) Gene Ontology analysis for the DEGs that were up‐regulated in 4‐1BB pos PD‐1 high CD8 + TILs compared to in 4‐1BB neg PD‐1 high CD8 + TILs. (C) Percentage of Ki‐67 + cells compared between 4‐1BB pos PD‐1 high and 4‐1BB neg PD‐1 high CD8 + TILs. Left panel shows representative flow cytometry plot. (D) Kaplan‐Meier curve comparing survival outcomes among subgroups (i.e., high and low 4‐1BB signature groups) of HCC patients in the TCGA cohort, according to expression of the 4‐1BB signature. Cutoff was determined by the maximal chi‐square method. (E) GSEA was performed to compare the enrichment of a T‐cell–inflamed gene signature between the high and low 4‐1BB signature groups. (F) Expression levels of parameters involved in T‐cell reinvigoration (i.e., TCF‐1, CD28, and T‐bet/Eomes) were compared between 4‐1BB pos PD‐1 high and 4‐1BB neg PD‐1 high CD8 + TILs. Left panel shows representative flow cytometry plots. * P < 0.05; *** P < 0.001. Abbreviations: ACKR4, atypical chemokine receptor 4; CEACAM1, carcinoembryonic antigen‐related cell adhesion molecule 1; CLEC1B, C‐type lectin domain family 1 member B; CMTM2, CKLF‐like MARVEL transmembrane domain‐containing 2; CXCL5, C‐X‐C motif chemokine ligand 5; Eomes, eomesodermin; GO, Gene Ontology; GZMA, granzyme 1, cytotoxic T‐lymphocyte–associated serine esterase 3; GZMK, granzyme K (serine protease, granzyme 3; tryptase II); IL2RA, interleukin‐2 receptor agonist; KLRB1, killer cell lectin‐like receptor B1; Max, maximum; ncRNA, noncoding RNA; NES, normalized enrichment score; NLRP13, NOD‐like receptor family pyrin domain containing 13; T‐bet, T‐box–containing protein expressed in T cells; TGFBR1, transforming growth factor beta receptor 1; tRNA, total RNA.

    Article Snippet: RNA‐sequencing (RNA‐seq) was performed on PD‐1 int , 4‐1BB neg PD‐1 high , and 4‐1BB pos PD‐1 high CD8 + TILs (n = 5) that were sorted using a FACS Aria II cell sorter (BD Biosciences), as well as on total CD8 + TILs sorted using CD8 Microbeads (n = 10; Miltenyi Biotec).

    Techniques: Expressing, Flow Cytometry

    4‐1BB costimulation enhances the function of CD8 + TILs, especially in HCCs exhibiting prominent T‐cell activation. (A) Investigation of the effect of 4‐1BB costimulation on the proliferative response of CD8 + TILs, as indicated by SI. (B,C,E) Study patients were subdivided into two subgroups using the median SI by anti–4‐1BB as the cutoff. (B) Comparison between the two subgroups of the relative increases of IFN‐γ and TNF‐α production by CD8 + TILs with 4‐1BB costimulation. (C) Comparison between the two subgroups of the percentages of 4‐1BB + , CD39 + CD103 + , CD38 + HLA‐DR + , and Ki‐67 + cells among CD8 + TILs. (D) Correlation between the percentage of 4‐1BB pos CD8 + TILs and the SI by 4‐1BB costimulation. (E) Receiver operating characteristic curve estimating the performance of the percentages of 4‐1BB pos CD8 + TILs with regard to distinguishing the two subgroups. Data are presented as mean ± SEM. (B,C) ** P < 0.01; *** P < 0.001. Abbreviation: Max, maximum.

    Journal: Hepatology (Baltimore, Md.)

    Article Title: 4‐1BB Delineates Distinct Activation Status of Exhausted Tumor‐Infiltrating CD8 + T Cells in Hepatocellular Carcinoma

    doi: 10.1002/hep.30881

    Figure Lengend Snippet: 4‐1BB costimulation enhances the function of CD8 + TILs, especially in HCCs exhibiting prominent T‐cell activation. (A) Investigation of the effect of 4‐1BB costimulation on the proliferative response of CD8 + TILs, as indicated by SI. (B,C,E) Study patients were subdivided into two subgroups using the median SI by anti–4‐1BB as the cutoff. (B) Comparison between the two subgroups of the relative increases of IFN‐γ and TNF‐α production by CD8 + TILs with 4‐1BB costimulation. (C) Comparison between the two subgroups of the percentages of 4‐1BB + , CD39 + CD103 + , CD38 + HLA‐DR + , and Ki‐67 + cells among CD8 + TILs. (D) Correlation between the percentage of 4‐1BB pos CD8 + TILs and the SI by 4‐1BB costimulation. (E) Receiver operating characteristic curve estimating the performance of the percentages of 4‐1BB pos CD8 + TILs with regard to distinguishing the two subgroups. Data are presented as mean ± SEM. (B,C) ** P < 0.01; *** P < 0.001. Abbreviation: Max, maximum.

    Article Snippet: RNA‐sequencing (RNA‐seq) was performed on PD‐1 int , 4‐1BB neg PD‐1 high , and 4‐1BB pos PD‐1 high CD8 + TILs (n = 5) that were sorted using a FACS Aria II cell sorter (BD Biosciences), as well as on total CD8 + TILs sorted using CD8 Microbeads (n = 10; Miltenyi Biotec).

    Techniques: Activation Assay, Comparison

    4‐1BB costimulation further enhances anti‐PD‐1–mediated CD8 + TIL reinvigoration. (A,B) Efficacy of the combination of 4‐1BB costimulation and PD‐1 blockade compared to the efficacy of PD‐1 blockade or isotype control in terms of proliferative response (A) and cytokine production (B). (C) Comparison of the proliferative functional response of CD8 + TILs with various combinations of PD‐1 blockade and costimulatory agonists (i.e., anti–4‐1BB, anti‐GITR, anti‐TNFR2, and anti‐CD30). (D) The percentage of 4‐1BB pos cells was compared between samples treated with PD‐1 blocking antibodies versus isotype control upon anti‐CD3 stimulation (10 ng/mL) for 48 hours. In (A) and (C), data are presented as the SI of CD8 + TILs. In (B), data are presented as the relative ratio of the percentage of CD8 + TILs that produce IFN‐γ and TNF‐α by combined 4‐1BB costimulation and PD‐1 blockade or PD‐1 blockade alone, compared to that by isotype control. ** P < 0.01; *** P < 0.001. Abbreviation: Max, maximum.

    Journal: Hepatology (Baltimore, Md.)

    Article Title: 4‐1BB Delineates Distinct Activation Status of Exhausted Tumor‐Infiltrating CD8 + T Cells in Hepatocellular Carcinoma

    doi: 10.1002/hep.30881

    Figure Lengend Snippet: 4‐1BB costimulation further enhances anti‐PD‐1–mediated CD8 + TIL reinvigoration. (A,B) Efficacy of the combination of 4‐1BB costimulation and PD‐1 blockade compared to the efficacy of PD‐1 blockade or isotype control in terms of proliferative response (A) and cytokine production (B). (C) Comparison of the proliferative functional response of CD8 + TILs with various combinations of PD‐1 blockade and costimulatory agonists (i.e., anti–4‐1BB, anti‐GITR, anti‐TNFR2, and anti‐CD30). (D) The percentage of 4‐1BB pos cells was compared between samples treated with PD‐1 blocking antibodies versus isotype control upon anti‐CD3 stimulation (10 ng/mL) for 48 hours. In (A) and (C), data are presented as the SI of CD8 + TILs. In (B), data are presented as the relative ratio of the percentage of CD8 + TILs that produce IFN‐γ and TNF‐α by combined 4‐1BB costimulation and PD‐1 blockade or PD‐1 blockade alone, compared to that by isotype control. ** P < 0.01; *** P < 0.001. Abbreviation: Max, maximum.

    Article Snippet: RNA‐sequencing (RNA‐seq) was performed on PD‐1 int , 4‐1BB neg PD‐1 high , and 4‐1BB pos PD‐1 high CD8 + TILs (n = 5) that were sorted using a FACS Aria II cell sorter (BD Biosciences), as well as on total CD8 + TILs sorted using CD8 Microbeads (n = 10; Miltenyi Biotec).

    Techniques: Comparison, Functional Assay, Blocking Assay