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Robe L Hendricks - One of the best experts on this subject based on the ideXlab platform.

  • pd l1 b7 h1 inhibits viral clearance by macrophages in hsv 1 infected corneas
    Journal of Immunology, 2018
    Co-Authors: Sohyu Jeo, Alexande M Rowe, Kate L Carroll, Stephe A K Harvey, Robe L Hendricks
    Abstract:

    Immune privilege helps protect the cornea from damaging inflammation but can also impair pathogen clearance from this mucosal surface. Programmed death-ligand 1 (PD-L1 or B7-H1) contributes to corneal immune privilege by inhibiting the function of a variety of immune cells. We asked whether programmed death-1 (PD-1)/PD-L1 interaction regulates HSV-1 clearance from infected corneas. We show that PD-L1 is constitutively expressed in the corneal epithelium and is upregulated upon HSV-1 corneal infection, with peak expression on CD45 + cells NK cells, dendritic cells, neutrophils, and macrophages and CD45 − corneal epithelial cells at 4 d postinfection (dpi). As early as 1 dpi, HSV-1–infected corneas of B7-H1 −/− mice as compared with wild-type mice showed increased chemokine expression and this correlated with increased migration of inflammatory cells into the viral lesions and decreased HSV-1 corneal titers. Local PD-L1 blockade caused a similar increase in viral clearance, suggesting a local effect of PD-1/PD-L1 in the cornea. The enhanced HSV-1 clearance at 2 dpi resulting from PD-1/PD-L1 blockade is mediated primarily by a monocyte/macrophage population. Studies in bone marrow chimeras demonstrated enhanced viral clearance when PD-L1 was absent only from nonhematopoietic cells. We conclude that PD-L1 expression on corneal cells negatively impacts the ability of the innate immune system to clear HSV-1 from infected corneas.

  • PD-L1/B7-H1 Inhibits Viral Clearance by Macrophages in HSV-1-Infected Corneas.
    Journal of Immunology, 2018
    Co-Authors: Sohyun Jeon, Alexande M Rowe, Kate L Carroll, Stephe A K Harvey, Robe L Hendricks
    Abstract:

    Immune privilege helps protect the cornea from damaging inflammation but can also impair pathogen clearance from this mucosal surface. Programmed death-ligand 1 (PD-L1 or B7-H1) contributes to corneal immune privilege by inhibiting the function of a variety of immune cells. We asked whether programmed death-1 (PD-1)/PD-L1 interaction regulates HSV-1 clearance from infected corneas. We show that PD-L1 is constitutively expressed in the corneal epithelium and is upregulated upon HSV-1 corneal infection, with peak expression on CD45 + cells NK cells, dendritic cells, neutrophils, and macrophages and CD45 − corneal epithelial cells at 4 d postinfection (dpi). As early as 1 dpi, HSV-1–infected corneas of B7-H1 −/− mice as compared with wild-type mice showed increased chemokine expression and this correlated with increased migration of inflammatory cells into the viral lesions and decreased HSV-1 corneal titers. Local PD-L1 blockade caused a similar increase in viral clearance, suggesting a local effect of PD-1/PD-L1 in the cornea. The enhanced HSV-1 clearance at 2 dpi resulting from PD-1/PD-L1 blockade is mediated primarily by a monocyte/macrophage population. Studies in bone marrow chimeras demonstrated enhanced viral clearance when PD-L1 was absent only from nonhematopoietic cells. We conclude that PD-L1 expression on corneal cells negatively impacts the ability of the innate immune system to clear HSV-1 from infected corneas.

  • programmed death ligand 1 expressed on corneal epithelium inhibits the local innate and adaptive immune response in the herpes simplex virus 1 infected cornea muc7p 751
    Journal of Immunology, 2014
    Co-Authors: Sohyun Jeon, Stephe A K Harvey, Robe L Hendricks
    Abstract:

    Constitutive expression of the PD-L1/B7-H1 ligand for the inhibitory receptor Programmed Death-1 (PD-1) appears to help protect the cornea from damaging inflammation, but might also limit clearance of pathogens from this mucosal surface. Indeed, mice lacking B7-H1 expression or those treated locally in the cornea with anti-PD-L1 mAb exhibited enhanced clearance of herpes simplex virus type 1 (HSV-1) from the cornea from 1 - 4 days post infection (dpi). PD-L1 expression peaked in the cornea on both CD45+ and CD45- cells at 4 dpi. Increased early viral clearance (1 dpi) was associated with significantly increased infiltration of CD45+ Gr-1+(presumed neutrophils) and increased production of the neutrophil chemokines CCL3 and CXCL1. Bone marrow chimeras that expressed PD-L1/B7-H1 only on bone marrow derived cells exhibited enhanced late viral clearance at 4 dpi in association with increased numbers of CD69+ CD3+ cells, but did not show enhanced early viral clearance at 1 dpi. Our findings suggest that PD-1 interacting with PD-L1/B7-H1 on CD45+ cells impairs early viral clearance from the cornea by inhibiting neutrophilic infiltration at 1 dpi, whereas PD-1 interacting with parenchymal cells (presumably corneal epithelial cells) inhibits late viral clearance by inhibiting T cell infiltration and/or activation at 3 dpi. Importantly, increasing viral clearance by inhibiting PD-1/PD-L1 interaction did not result in observable inflammatory damage to the cornea.

Christian Pfister - One of the best experts on this subject based on the ideXlab platform.

  • clinical interest of pd l1 immuno histochemistry expression as a predictive factor of bacillus calmette guerin bcg efficacy in refractory high risk non muscle invasive bladder cancer nmibc
    World Journal of Urology, 2020
    Co-Authors: Clara Delcourt, Sophie Ferlicot, Pierre Gemival, François Xavier Nouhaud, Françoise Gobet, Andre Gillibert, Jean Christophe Sabourin, Jacques Irani, Christian Pfister
    Abstract:

    OBJECTIVE: To assess PD-L1 expression in tumor (TC) and tumor infiltrating immune cells (IC) as a predictive factor of BCG therapy failure in high-risk NMIBC. MATERIALS AND METHODS: Patients treated with complete resection followed by bladder BCG instillation for high-risk NMIBC were included. Early recurrence (ER) was defined as tumor recurrence after BCG induction course. The association between ER and immuno-histochemistry PD-L1 (E1L3N clone) expression by tumors cells (TC) and tumor infiltrating immune cells (IC) was investigated using an exact Fisher test variant. RESULTS: A total of 186 patients were included, of whom 38 (20.4%) were ER, 35 (18.8%) were positive for TC PD-L1 expression and 60 (32.3%) were positive for IC PD-L1. ER was not significantly (p = 0.97) more frequent in the TC PD-L1 ≥ 1% group (n = 7, 20.0%) than in the TC PD-L1-negative group (n = 31, 20.5%). Patients with IC PD-L1 negative had ER in 15 (19.2%) cases and patients with IC PD-L1 ≥ 1% had ER in 23 (21.3%) cases. PD-L1-positive expression for IC (threshold > 1%) was correlated with immune infiltrate density (95.2% dense immune infiltrate vs 47.2% low immune infiltrate, p < 0.05), with increased expression of PD-L1 by IC after BCG therapy (p = 0.006). CONCLUSION: No association was observed between immuno-histochemistry PD-L1 positivity and ER after BCG therapy. Nevertheless, the relationship between immune infiltrate and PD-L1 positivity confirmed the interest of assessing the immune infiltrate density to define tumor's profile.

  • Clinical interest of PD-L1 immuno-histochemistry expression as a predictive factor of Bacillus Calmette Guerin (BCG) efficacy in refractory high-risk non-muscle-invasive bladder cancer (NMIBC)
    World Journal of Urology, 2019
    Co-Authors: Clara Delcourt, Sophie Ferlicot, Pierre Gemival, François Xavier Nouhaud, Françoise Gobet, Andre Gillibert, Jean Christophe Sabourin, Jacques Irani, Christian Pfister
    Abstract:

    Objective To assess PD-L1 expression in tumor (TC) and tumor infiltrating immune cells (IC) as a predictive factor of BCG therapy failure in high-risk NMIBC. Materials and methods Patients treated with complete resection followed by bladder BCG instillation for high-risk NMIBC were included. Early recurrence (ER) was defined as tumor recurrence after BCG induction course. The association between ER and immuno-histochemistry PD-L1 (E1L3N clone) expression by tumors cells (TC) and tumor infiltrating immune cells (IC) was investigated using an exact Fisher test variant. Results A total of 186 patients were included, of whom 38 (20.4%) were ER, 35 (18.8%) were positive for TC PD-L1 expression and 60 (32.3%) were positive for IC PD-L1. ER was not significantly ( p  = 0.97) more frequent in the TC PD-L1 ≥ 1% group ( n  = 7, 20.0%) than in the TC PD-L1-negative group ( n  = 31, 20.5%). Patients with IC PD-L1 negative had ER in 15 (19.2%) cases and patients with IC PD-L1 ≥ 1% had ER in 23 (21.3%) cases. PD-L1-positive expression for IC (threshold > 1%) was correlated with immune infiltrate density (95.2% dense immune infiltrate vs 47.2% low immune infiltrate, p  

Sophie Ferlicot - One of the best experts on this subject based on the ideXlab platform.

  • clinical interest of pd l1 immuno histochemistry expression as a predictive factor of bacillus calmette guerin bcg efficacy in refractory high risk non muscle invasive bladder cancer nmibc
    World Journal of Urology, 2020
    Co-Authors: Clara Delcourt, Sophie Ferlicot, Pierre Gemival, François Xavier Nouhaud, Françoise Gobet, Andre Gillibert, Jean Christophe Sabourin, Jacques Irani, Christian Pfister
    Abstract:

    OBJECTIVE: To assess PD-L1 expression in tumor (TC) and tumor infiltrating immune cells (IC) as a predictive factor of BCG therapy failure in high-risk NMIBC. MATERIALS AND METHODS: Patients treated with complete resection followed by bladder BCG instillation for high-risk NMIBC were included. Early recurrence (ER) was defined as tumor recurrence after BCG induction course. The association between ER and immuno-histochemistry PD-L1 (E1L3N clone) expression by tumors cells (TC) and tumor infiltrating immune cells (IC) was investigated using an exact Fisher test variant. RESULTS: A total of 186 patients were included, of whom 38 (20.4%) were ER, 35 (18.8%) were positive for TC PD-L1 expression and 60 (32.3%) were positive for IC PD-L1. ER was not significantly (p = 0.97) more frequent in the TC PD-L1 ≥ 1% group (n = 7, 20.0%) than in the TC PD-L1-negative group (n = 31, 20.5%). Patients with IC PD-L1 negative had ER in 15 (19.2%) cases and patients with IC PD-L1 ≥ 1% had ER in 23 (21.3%) cases. PD-L1-positive expression for IC (threshold > 1%) was correlated with immune infiltrate density (95.2% dense immune infiltrate vs 47.2% low immune infiltrate, p < 0.05), with increased expression of PD-L1 by IC after BCG therapy (p = 0.006). CONCLUSION: No association was observed between immuno-histochemistry PD-L1 positivity and ER after BCG therapy. Nevertheless, the relationship between immune infiltrate and PD-L1 positivity confirmed the interest of assessing the immune infiltrate density to define tumor's profile.

  • Clinical interest of PD-L1 immuno-histochemistry expression as a predictive factor of Bacillus Calmette Guerin (BCG) efficacy in refractory high-risk non-muscle-invasive bladder cancer (NMIBC)
    World Journal of Urology, 2019
    Co-Authors: Clara Delcourt, Sophie Ferlicot, Pierre Gemival, François Xavier Nouhaud, Françoise Gobet, Andre Gillibert, Jean Christophe Sabourin, Jacques Irani, Christian Pfister
    Abstract:

    Objective To assess PD-L1 expression in tumor (TC) and tumor infiltrating immune cells (IC) as a predictive factor of BCG therapy failure in high-risk NMIBC. Materials and methods Patients treated with complete resection followed by bladder BCG instillation for high-risk NMIBC were included. Early recurrence (ER) was defined as tumor recurrence after BCG induction course. The association between ER and immuno-histochemistry PD-L1 (E1L3N clone) expression by tumors cells (TC) and tumor infiltrating immune cells (IC) was investigated using an exact Fisher test variant. Results A total of 186 patients were included, of whom 38 (20.4%) were ER, 35 (18.8%) were positive for TC PD-L1 expression and 60 (32.3%) were positive for IC PD-L1. ER was not significantly ( p  = 0.97) more frequent in the TC PD-L1 ≥ 1% group ( n  = 7, 20.0%) than in the TC PD-L1-negative group ( n  = 31, 20.5%). Patients with IC PD-L1 negative had ER in 15 (19.2%) cases and patients with IC PD-L1 ≥ 1% had ER in 23 (21.3%) cases. PD-L1-positive expression for IC (threshold > 1%) was correlated with immune infiltrate density (95.2% dense immune infiltrate vs 47.2% low immune infiltrate, p  

  • Renal Cell Carcinoma Programmed Death-ligand 1, a New Direct Target of Hypoxia-inducible Factor-2 Alpha, is Regulated by von Hippel-Lindau Gene Mutation Status
    European Urology, 2016
    Co-Authors: Yosra Messai, Sophie Gad, Muhammad Zaeem Noman, Gwenael Le Teuff, Sophie Couve, Bassam Janji, Solenne Florence Kammerer, Nathalie Rioux-leclerc, Meriem Hasmim, Sophie Ferlicot
    Abstract:

    BACKGROUND: Clear cell renal cell carcinomas (ccRCC) frequently display a loss of function of the von Hippel-Lindau (VHL) gene. OBJECTIVE: To elucidate the putative relationship between VHL mutation status and immune checkpoint ligand programmed death-ligand 1 (PD-L1) expression. DESIGN, SETTING, AND PARTICIPANTS: A series of 32 renal tumors composed of 11 VHL tumor-associated and 21 sporadic RCCs were used to evaluate PD-L1 expression levels after sequencing of the three exons and exon-intron junctions of the VHL gene. The 786-O, A498, and RCC4 cell lines were used to investigate the mechanisms of PD-L1 regulation. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Fisher's exact test was used for VHL mutation and Kruskal-Wallis test for PD-L1 expression. If no covariate accounted for the association of VHL and PD-L1, then a Kruskal-Wallis test was used; otherwise Cochran-Mantel-Haenzsel test was used. We also used the Fligner-Policello test to compare two medians when the distributions had different dispersions. RESULTS AND LIMITATIONS: We demonstrated that tumors from ccRCC patients with VHL biallelic inactivation (ie, loss of function) display a significant increase in PD-L1 expression compared with ccRCC tumors carrying one VHL wild-type allele. Using the inducible VHL 786-O-derived cell lines with varying hypoxia-inducible factor-2 alpha (HIF-2α) stabilization levels, we showed that PD-L1 expression levels positively correlate with VHL mutation and HIF-2α expression. Targeting HIF-2α decreased PD-L1, while HIF-2α overexpression increased PD-L1 mRNA and protein levels in ccRCC cells. Interestingly, chromatin immunoprecipitation and luciferase assays revealed a direct binding of HIF-2α to a transcriptionally active hypoxia-response element in the human PD-L1 proximal promoter in 786-O cells. CONCLUSIONS: Our work provides the first evidence that VHL mutations positively correlate with PD-L1 expression in ccRCC and may influence the response to ccRCC anti-PD-L1/PD-1 immunotherapy. PATIENT SUMMARY: We investigated the relationship between von Hippel-Lindau mutations and programmed death-ligand 1 expression. We demonstrated that von Hippel-Lindau mutation status significantly correlated with programmed death-ligand 1 expression in clear cell renal cell carcinomas

Toyonori Tsuzuki - One of the best experts on this subject based on the ideXlab platform.

  • Clinicopathological analysis of neoplastic PD-L1-positive EBV^+ diffuse large B cell lymphoma, not otherwise specified, in a Japanese cohort
    Virchows Archiv, 2020
    Co-Authors: Taishi Takahara, Akira Satou, Eri Ishikawa, Kei Kohno, Seiichi Kato, Yuka Suzuki, Emiko Takahashi, Akiko Ohashi, Naoko Asano, Toyonori Tsuzuki
    Abstract:

    The programmed death 1 (PD1)/PD1 ligand (PD-L1) axis plays an important role in the pathogenesis of Epstein-Barr virus-positive diffuse large B cell lymphoma, not otherwise specified (EBV+ DLBCL, NOS). Here, we describe PD-L1 expression by EBV+ DLBCL, NOS in order to evaluate its possible contribution to the pathogenesis of this tumor. The study included 57 cases of EBV+ DLBCL, NOS. The median patient age was 69 years and 95% ( n  = 54) were aged > 45. Extranodal lesions were present in 39 (69%) at initial diagnosis. PD-L1 expression (mAb SP142-positive staining) was present in more than 5% of tumor cells in only six cases (11%), in clear contrast to the 77% reported in cases aged under 45 years. Among the PD-L1+ cases, three were nodal lesions. All six PD-L1+ cases progressed in the 3 years after diagnosis and four of the six patients died of the disease within 2 years. PD-L1+ cases had significantly shorter PFS ( P  = 0.002) and relatively short OS ( P  = 0.26), compared with PD-L1− cases. EBV+ DLBCL, NOS in the elderly infrequently expressed PD-L1 and had poor prognosis. PD-L1 expression in EBV+ DLBCL, NOS of the elderly sheds light on the pathogenetic role of immune senescence.

  • Clinicopathological analysis of neoplastic PD-L1-positive EBV^+ diffuse large B cell lymphoma, not otherwise specified, in a Japanese cohort
    Virchows Archiv, 2020
    Co-Authors: Taishi Takahara, Akira Satou, Eri Ishikawa, Kei Kohno, Seiichi Kato, Yuka Suzuki, Emiko Takahashi, Akiko Ohashi, Naoko Asano, Toyonori Tsuzuki
    Abstract:

    The programmed death 1 (PD1)/PD1 ligand (PD-L1) axis plays an important role in the pathogenesis of Epstein-Barr virus-positive diffuse large B cell lymphoma, not otherwise specified (EBV+ DLBCL, NOS). Here, we describe PD-L1 expression by EBV+ DLBCL, NOS in order to evaluate its possible contribution to the pathogenesis of this tumor. The study included 57 cases of EBV+ DLBCL, NOS. The median patient age was 69 years and 95% ( n  = 54) were aged > 45. Extranodal lesions were present in 39 (69%) at initial diagnosis. PD-L1 expression (mAb SP142-positive staining) was present in more than 5% of tumor cells in only six cases (11%), in clear contrast to the 77% reported in cases aged under 45 years. Among the PD-L1+ cases, three were nodal lesions. All six PD-L1+ cases progressed in the 3 years after diagnosis and four of the six patients died of the disease within 2 years. PD-L1+ cases had significantly shorter PFS ( P  = 0.002) and relatively short OS ( P  = 0.26), compared with PD-L1− cases. EBV+ DLBCL, NOS in the elderly infrequently expressed PD-L1 and had poor prognosis. PD-L1 expression in EBV+ DLBCL, NOS of the elderly sheds light on the pathogenetic role of immune senescence.

Clara Delcourt - One of the best experts on this subject based on the ideXlab platform.

  • clinical interest of pd l1 immuno histochemistry expression as a predictive factor of bacillus calmette guerin bcg efficacy in refractory high risk non muscle invasive bladder cancer nmibc
    World Journal of Urology, 2020
    Co-Authors: Clara Delcourt, Sophie Ferlicot, Pierre Gemival, François Xavier Nouhaud, Françoise Gobet, Andre Gillibert, Jean Christophe Sabourin, Jacques Irani, Christian Pfister
    Abstract:

    OBJECTIVE: To assess PD-L1 expression in tumor (TC) and tumor infiltrating immune cells (IC) as a predictive factor of BCG therapy failure in high-risk NMIBC. MATERIALS AND METHODS: Patients treated with complete resection followed by bladder BCG instillation for high-risk NMIBC were included. Early recurrence (ER) was defined as tumor recurrence after BCG induction course. The association between ER and immuno-histochemistry PD-L1 (E1L3N clone) expression by tumors cells (TC) and tumor infiltrating immune cells (IC) was investigated using an exact Fisher test variant. RESULTS: A total of 186 patients were included, of whom 38 (20.4%) were ER, 35 (18.8%) were positive for TC PD-L1 expression and 60 (32.3%) were positive for IC PD-L1. ER was not significantly (p = 0.97) more frequent in the TC PD-L1 ≥ 1% group (n = 7, 20.0%) than in the TC PD-L1-negative group (n = 31, 20.5%). Patients with IC PD-L1 negative had ER in 15 (19.2%) cases and patients with IC PD-L1 ≥ 1% had ER in 23 (21.3%) cases. PD-L1-positive expression for IC (threshold > 1%) was correlated with immune infiltrate density (95.2% dense immune infiltrate vs 47.2% low immune infiltrate, p < 0.05), with increased expression of PD-L1 by IC after BCG therapy (p = 0.006). CONCLUSION: No association was observed between immuno-histochemistry PD-L1 positivity and ER after BCG therapy. Nevertheless, the relationship between immune infiltrate and PD-L1 positivity confirmed the interest of assessing the immune infiltrate density to define tumor's profile.

  • Clinical interest of PD-L1 immuno-histochemistry expression as a predictive factor of Bacillus Calmette Guerin (BCG) efficacy in refractory high-risk non-muscle-invasive bladder cancer (NMIBC)
    World Journal of Urology, 2019
    Co-Authors: Clara Delcourt, Sophie Ferlicot, Pierre Gemival, François Xavier Nouhaud, Françoise Gobet, Andre Gillibert, Jean Christophe Sabourin, Jacques Irani, Christian Pfister
    Abstract:

    Objective To assess PD-L1 expression in tumor (TC) and tumor infiltrating immune cells (IC) as a predictive factor of BCG therapy failure in high-risk NMIBC. Materials and methods Patients treated with complete resection followed by bladder BCG instillation for high-risk NMIBC were included. Early recurrence (ER) was defined as tumor recurrence after BCG induction course. The association between ER and immuno-histochemistry PD-L1 (E1L3N clone) expression by tumors cells (TC) and tumor infiltrating immune cells (IC) was investigated using an exact Fisher test variant. Results A total of 186 patients were included, of whom 38 (20.4%) were ER, 35 (18.8%) were positive for TC PD-L1 expression and 60 (32.3%) were positive for IC PD-L1. ER was not significantly ( p  = 0.97) more frequent in the TC PD-L1 ≥ 1% group ( n  = 7, 20.0%) than in the TC PD-L1-negative group ( n  = 31, 20.5%). Patients with IC PD-L1 negative had ER in 15 (19.2%) cases and patients with IC PD-L1 ≥ 1% had ER in 23 (21.3%) cases. PD-L1-positive expression for IC (threshold > 1%) was correlated with immune infiltrate density (95.2% dense immune infiltrate vs 47.2% low immune infiltrate, p