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  1. Article ; Online: Humoral complementomics - exploration of noninvasive complement biomarkers as predictors of renal cancer progression.

    Revel, Margot / Rezola Artero, Mikel / Hamidi, Houcine / Grunenwald, Anne / Blasco, Loris / Vano, Yann A / Marie Oudard, Stephane / Sanchez-Salas, Rafael / Macek, Petr / Rodriguez Sanchez, Lara / Cathelineau, Xavier / Vedié, Benoit / Sautes-Fridman, Catherine / Herman Fridman, Wolf / Roumenina, Lubka T / Dragon-Durey, Marie-Agnes

    Oncoimmunology

    2024  Volume 13, Issue 1, Page(s) 2328433

    Abstract: Despite the progress of anti-cancer treatment, the prognosis of many patients with solid tumors is still dismal. Reliable noninvasive biomarkers are needed to predict patient survival and therapy response. Here, we propose ... ...

    Abstract Despite the progress of anti-cancer treatment, the prognosis of many patients with solid tumors is still dismal. Reliable noninvasive biomarkers are needed to predict patient survival and therapy response. Here, we propose a
    MeSH term(s) Humans ; Carcinoma, Renal Cell/diagnosis ; Prospective Studies ; Kidney Neoplasms/diagnosis ; Kidney Neoplasms/metabolism ; Biomarkers/metabolism ; Autoantibodies
    Chemical Substances Biomarkers ; Autoantibodies
    Language English
    Publishing date 2024-03-13
    Publishing country United States
    Document type Journal Article
    ZDB-ID 2645309-5
    ISSN 2162-402X ; 2162-402X
    ISSN (online) 2162-402X
    ISSN 2162-402X
    DOI 10.1080/2162402X.2024.2328433
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  2. Article ; Online: Mesenchymal-like Tumor Cells and Myofibroblastic Cancer-Associated Fibroblasts Are Associated with Progression and Immunotherapy Response of Clear Cell Renal Cell Carcinoma.

    Davidson, Guillaume / Helleux, Alexandra / Vano, Yann A / Lindner, Véronique / Fattori, Antonin / Cerciat, Marie / Elaidi, Reza T / Verkarre, Virginie / Sun, Cheng-Ming / Chevreau, Christine / Bennamoun, Mostefa / Lang, Hervé / Tricard, Thibault / Fridman, Wolf H / Sautes-Fridman, Catherine / Su, Xiaoping / Plassard, Damien / Keime, Celine / Thibault-Carpentier, Christelle /
    Barthelemy, Philippe / Oudard, Stéphane M / Davidson, Irwin / Malouf, Gabriel G

    Cancer research

    2023  Volume 83, Issue 17, Page(s) 2952–2969

    Abstract: Immune checkpoint inhibitors (ICI) represent the cornerstone for the treatment of patients with metastatic clear cell renal cell carcinoma (ccRCC). Despite a favorable response for a subset of patients, others experience primary progressive disease, ... ...

    Abstract Immune checkpoint inhibitors (ICI) represent the cornerstone for the treatment of patients with metastatic clear cell renal cell carcinoma (ccRCC). Despite a favorable response for a subset of patients, others experience primary progressive disease, highlighting the need to precisely understand the plasticity of cancer cells and their cross-talk with the microenvironment to better predict therapeutic response and personalize treatment. Single-cell RNA sequencing of ccRCC at different disease stages and normal adjacent tissue (NAT) from patients identified 46 cell populations, including 5 tumor subpopulations, characterized by distinct transcriptional signatures representing an epithelial-to-mesenchymal transition gradient and a novel inflamed state. Deconvolution of the tumor and microenvironment signatures in public data sets and data from the BIONIKK clinical trial (NCT02960906) revealed a strong correlation between mesenchymal-like ccRCC cells and myofibroblastic cancer-associated fibroblasts (myCAF), which are both enriched in metastases and correlate with poor patient survival. Spatial transcriptomics and multiplex immune staining uncovered the spatial proximity of mesenchymal-like ccRCC cells and myCAFs at the tumor-NAT interface. Moreover, enrichment in myCAFs was associated with primary resistance to ICI therapy in the BIONIKK clinical trial. These data highlight the epithelial-mesenchymal plasticity of ccRCC cancer cells and their relationship with myCAFs, a critical component of the microenvironment associated with poor outcome and ICI resistance.
    Significance: Single-cell and spatial transcriptomics reveal the proximity of mesenchymal tumor cells to myofibroblastic cancer-associated fibroblasts and their association with disease outcome and immune checkpoint inhibitor response in clear cell renal cell carcinoma.
    MeSH term(s) Humans ; Cancer-Associated Fibroblasts/pathology ; Carcinoma, Renal Cell/drug therapy ; Carcinoma, Renal Cell/genetics ; Gene Expression Profiling ; Immunotherapy ; Kidney Neoplasms/drug therapy ; Kidney Neoplasms/genetics ; Prognosis ; Tumor Microenvironment ; Clinical Trials as Topic
    Language English
    Publishing date 2023-06-18
    Publishing country United States
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 1432-1
    ISSN 1538-7445 ; 0008-5472
    ISSN (online) 1538-7445
    ISSN 0008-5472
    DOI 10.1158/0008-5472.CAN-22-3034
    Database MEDical Literature Analysis and Retrieval System OnLINE

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    Uh III Zs.135/5: Show issues Location:
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  3. Article ; Online: Transcriptomic analysis of the tumor microenvironment to guide prognosis and immunotherapies.

    Petitprez, Florent / Vano, Yann A / Becht, Etienne / Giraldo, Nicolas A / de Reyniès, Aurélien / Sautès-Fridman, Catherine / Fridman, Wolf H

    Cancer immunology, immunotherapy : CII

    2017  Volume 67, Issue 6, Page(s) 981–988

    Abstract: Tumors are highly heterogeneous tissues where malignant cells are surrounded by and interact with a complex tumor microenvironment (TME), notably composed of a wide variety of immune cells, as well as vessels and fibroblasts. As the dialectical influence ...

    Abstract Tumors are highly heterogeneous tissues where malignant cells are surrounded by and interact with a complex tumor microenvironment (TME), notably composed of a wide variety of immune cells, as well as vessels and fibroblasts. As the dialectical influence between tumor cells and their TME is known to be clinically crucial, we need tools that allow us to study the cellular composition of the microenvironment. In this focused research review, we report MCP-counter, a methodology based on transcriptomic markers that assesses the proportion of several immune and stromal cell populations in the TME from transcriptomic data, and we highlight how it can provide a way to decipher the complex mechanisms at play in tumors. In several malignancies, MCP-counter scores have been used to show various prognostic impacts of the TME, which we also show to be linked with the mutational burden of tumors. We also compared established molecular classifications of colorectal cancer and clear-cell renal cell carcinoma with the output of MCP-counter, and show that molecular subgroups have different TME profiles, and that these profiles are consistent within a given subgroup. Finally, we provide insights as to how knowing the TME composition may shape patient care in the near future.
    MeSH term(s) Gene Expression Profiling ; Humans ; Immunotherapy/methods ; Prognosis ; Tumor Microenvironment
    Language English
    Publishing date 2017-09-07
    Publishing country Germany
    Document type Journal Article ; Research Support, Non-U.S. Gov't ; Review
    ZDB-ID 195342-4
    ISSN 1432-0851 ; 0340-7004
    ISSN (online) 1432-0851
    ISSN 0340-7004
    DOI 10.1007/s00262-017-2058-z
    Database MEDical Literature Analysis and Retrieval System OnLINE

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    Zs.A 1237: Show issues Location:
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  4. Article ; Online: Plasma CD27, a Surrogate of the Intratumoral CD27-CD70 Interaction, Correlates with Immunotherapy Resistance in Renal Cell Carcinoma.

    Benhamouda, Nadine / Sam, Ikuan / Epaillard, Nicolas / Gey, Alain / Phan, Letuan / Pham, Hang Phuong / Gruel, Nadège / Saldmann, Antonin / Pineau, Joséphine / Hasan, Milena / Quiniou, Valentin / Nevoret, Camille / Verkarre, Virginie / Libri, Valentina / Mella, Sebastien / Granier, Clémence / Broudin, Chloe / Ravel, Patrice / De Guillebon, Eléonore /
    Mauge, Laetitia / Helley, Dominique / Jabla, Bernd / Chaput, Nathalie / Albiges, Laurence / Katsahian, Sandrine / Adam, Julien / Mejean, Arnaud / Adotevi, Olivier / Vano, Yann A / Oudard, Stéphane / Tartour, Eric

    Clinical cancer research : an official journal of the American Association for Cancer Research

    2022  Volume 28, Issue 22, Page(s) 4983–4994

    Abstract: Purpose: CD70 is a costimulatory molecule known to activate CD27-expressing T cells. CD27-CD70 interaction leads to the release of soluble CD27 (sCD27). Clear-cell renal cell carcinoma (ccRCC) expresses the highest levels of CD70 among all solid tumors; ...

    Abstract Purpose: CD70 is a costimulatory molecule known to activate CD27-expressing T cells. CD27-CD70 interaction leads to the release of soluble CD27 (sCD27). Clear-cell renal cell carcinoma (ccRCC) expresses the highest levels of CD70 among all solid tumors; however, the clinical consequences of CD70 expression remain unclear.
    Experimental design: Tumor tissue from 25 patients with ccRCC was assessed for the expression of CD27 and CD70 in situ using multiplex immunofluorescence. CD27+ T-cell phenotypes in tumors were analyzed by flow cytometry and their gene expression profile were analyzed by single-cell RNA sequencing then confirmed with public data. Baseline sCD27 was measured in 81 patients with renal cell carcinoma (RCC) treated with immunotherapy (35 for training cohort and 46 for validation cohort).
    Results: In the tumor microenvironment, CD27+ T cells interacted with CD70-expressing tumor cells. Compared with CD27- T cells, CD27+ T cells exhibited an apoptotic and dysfunctional signature. In patients with RCC, the intratumoral CD27-CD70 interaction was significantly correlated with the plasma sCD27 concentration. High sCD27 levels predicted poor overall survival in patients with RCC treated with anti-programmed cell death protein 1 in both the training and validation cohorts but not in patients treated with antiangiogenic therapy.
    Conclusions: In conclusion, we demonstrated that sCD27, a surrogate marker of T-cell dysfunction, is a predictive biomarker of resistance to immunotherapy in RCC. Given the frequent expression of CD70 and CD27 in solid tumors, our findings may be extended to other tumors.
    MeSH term(s) Humans ; Carcinoma, Renal Cell/drug therapy ; Carcinoma, Renal Cell/genetics ; CD27 Ligand/genetics ; Tumor Necrosis Factor Receptor Superfamily, Member 7/genetics ; Immunotherapy ; Kidney Neoplasms/drug therapy ; Kidney Neoplasms/genetics ; Tumor Microenvironment
    Chemical Substances CD27 Ligand ; Tumor Necrosis Factor Receptor Superfamily, Member 7 ; CD70 protein, human
    Language English
    Publishing date 2022-09-06
    Publishing country United States
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 1225457-5
    ISSN 1557-3265 ; 1078-0432
    ISSN (online) 1557-3265
    ISSN 1078-0432
    DOI 10.1158/1078-0432.CCR-22-0905
    Database MEDical Literature Analysis and Retrieval System OnLINE

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    In stock of ZB MED Cologne/Königswinter

    Zs.A 4223: Show issues Location:
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  5. Article ; Online: Complement C1s and C4d as Prognostic Biomarkers in Renal Cancer: Emergence of Noncanonical Functions of C1s.

    Daugan, Marie V / Revel, Margot / Russick, Jules / Dragon-Durey, Marie-Agnès / Gaboriaud, Christine / Robe-Rybkine, Tania / Poillerat, Victoria / Grunenwald, Anne / Lacroix, Guillaume / Bougouin, Antoine / Meylan, Maxime / Verkarre, Virginie / Oudard, Stephane M / Mejean, Arnaud / Vano, Yann A / Perkins, Geraldine / Validire, Pierre / Cathelineau, Xavier / Sanchez-Salas, Rafael /
    Damotte, Diane / Fremeaux-Bacchi, Veronique / Cremer, Isabelle / Sautès-Fridman, Catherine / Fridman, Wolf H / Roumenina, Lubka T

    Cancer immunology research

    2021  Volume 9, Issue 8, Page(s) 891–908

    Abstract: The complement system plays a complex role in cancer. In clear cell renal cell carcinoma (ccRCC), local production of complement proteins drives tumor progression, but the mechanisms by which they do this are poorly understood. We found that complement ... ...

    Abstract The complement system plays a complex role in cancer. In clear cell renal cell carcinoma (ccRCC), local production of complement proteins drives tumor progression, but the mechanisms by which they do this are poorly understood. We found that complement activation, as reflected by high plasma C4d or as C4d deposits at the tumor site, was associated with poor prognosis in two cohorts of patients with ccRCC. High expression of the C4-activating enzyme C1s by tumor cells was associated with poor prognosis in three cohorts. Multivariate Cox analysis revealed that the prognostic value of C1s was independent from complement deposits, suggesting the possibility of complement cascade-unrelated, protumoral functions for C1s. Silencing of C1s in cancer cell lines resulted in decreased proliferation and viability of the cells and in increased activation of T cells in
    MeSH term(s) Animals ; Biomarkers, Tumor/metabolism ; Case-Control Studies ; Complement C1s/metabolism ; Complement C4/metabolism ; Humans ; Kidney Neoplasms/genetics ; Mice ; Prognosis ; Prospective Studies ; Transfection
    Chemical Substances Biomarkers, Tumor ; Complement C4 ; Complement C1s (EC 3.4.21.42)
    Language English
    Publishing date 2021-05-26
    Publishing country United States
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 2732489-8
    ISSN 2326-6074 ; 2326-6066
    ISSN (online) 2326-6074
    ISSN 2326-6066
    DOI 10.1158/2326-6066.CIR-20-0532
    Database MEDical Literature Analysis and Retrieval System OnLINE

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    Zs.A 7022: Show issues Location:
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  6. Article ; Online: Tumor Cells Hijack Macrophage-Produced Complement C1q to Promote Tumor Growth.

    Roumenina, Lubka T / Daugan, Marie V / Noé, Rémi / Petitprez, Florent / Vano, Yann A / Sanchez-Salas, Rafaël / Becht, Etienne / Meilleroux, Julie / Clec'h, Bénédicte Le / Giraldo, Nicolas A / Merle, Nicolas S / Sun, Cheng-Ming / Verkarre, Virginie / Validire, Pierre / Selves, Janick / Lacroix, Laetitia / Delfour, Olivier / Vandenberghe, Isabelle / Thuilliez, Celine /
    Keddani, Sonia / Sakhi, Imene B / Barret, Eric / Ferré, Pierre / Corvaïa, Nathalie / Passioukov, Alexandre / Chetaille, Eric / Botto, Marina / de Reynies, Aurélien / Oudard, Stephane Marie / Mejean, Arnaud / Cathelineau, Xavier / Sautès-Fridman, Catherine / Fridman, Wolf H

    Cancer immunology research

    2019  Volume 7, Issue 7, Page(s) 1091–1105

    Abstract: Clear-cell renal cell carcinoma (ccRCC) possesses an unmet medical need, particularly at the metastatic stage, when surgery is ineffective. Complement is a key factor in tissue inflammation, favoring cancer progression through the production of ... ...

    Abstract Clear-cell renal cell carcinoma (ccRCC) possesses an unmet medical need, particularly at the metastatic stage, when surgery is ineffective. Complement is a key factor in tissue inflammation, favoring cancer progression through the production of complement component 5a (C5a). However, the activation pathways that generate C5a in tumors remain obscure. By data mining, we identified ccRCC as a cancer type expressing concomitantly high expression of the components that are part of the classical complement pathway. To understand how the complement cascade is activated in ccRCC and impacts patients' clinical outcome, primary tumors from three patient cohorts (
    MeSH term(s) Animals ; Apoptosis ; Carcinoma, Renal Cell/immunology ; Carcinoma, Renal Cell/metabolism ; Carcinoma, Renal Cell/pathology ; Cell Proliferation ; Complement Activation ; Complement C1q/immunology ; Complement C1q/metabolism ; Complement C3/immunology ; Complement C3/metabolism ; Complement C4/immunology ; Complement C4/metabolism ; Female ; Follow-Up Studies ; Humans ; Immunologic Factors/metabolism ; Kidney Neoplasms/immunology ; Kidney Neoplasms/metabolism ; Kidney Neoplasms/pathology ; Macrophages/immunology ; Male ; Mice ; Mice, Inbred C57BL ; Mice, Knockout ; Middle Aged ; Prognosis ; Prospective Studies ; Retrospective Studies ; Survival Rate ; Tumor Cells, Cultured ; Tumor Microenvironment/immunology
    Chemical Substances Complement C3 ; Complement C4 ; Immunologic Factors ; Complement C1q (80295-33-6)
    Language English
    Publishing date 2019-06-04
    Publishing country United States
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 2732489-8
    ISSN 2326-6074 ; 2326-6066
    ISSN (online) 2326-6074
    ISSN 2326-6066
    DOI 10.1158/2326-6066.CIR-18-0891
    Database MEDical Literature Analysis and Retrieval System OnLINE

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