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Questions {❓}

• PD-L1 biomarker testing for non-small cell lung cancer: truth or fiction?

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         headline:Thoracic and cutaneous sarcoid-like reaction associated with anti-PD-1 therapy: longitudinal monitoring of PD-1 and PD-L1 expression after stopping treatment
         description:Immune checkpoint inhibitors (ICI) target T cell inhibitory pathways that are responsible for cancer tolerance by down-modulating immune functions. ICI have revolutionized patients care with lung cancer. Nevertheless, restoring endogenous antitumor T-cell responses can induce immune related adverse events, such as sarcoidosis. We report here the first case of a thoracic and cutaneous sarcoid-like reaction in a patient with a relapsing unresectable non-small cell lung cancer (NSCLC) treated with nivolumab, an anti-PD-1 mAb. The expression of PD-1 and its ligands, PD-L1 and PD-L2, was assessed by flow cytometry on peripheral blood mononuclear cells (PBMC) and compared to patients who had discontinued nivolumab therapy without having developed any immune related adverse events. PD-L1 expression was transiently increased on B cells, T cells and monocytes, whereas PD-L2 expression was not modulated. PD-1 was transiently undetectable when PD-L1 was maximal, before returning to basal level. Sarcoidosis spontaneously resolved, without corticotherapy. This case sheds the light on a complex regulation of PD-L1 expression in vivo on PBMC after nivolumab arrest and triggers the question of monitoring the expression of immune checkpoint on immune cells during and after treatment with ICI.
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      headline:Thoracic and cutaneous sarcoid-like reaction associated with anti-PD-1 therapy: longitudinal monitoring of PD-1 and PD-L1 expression after stopping treatment
      description:Immune checkpoint inhibitors (ICI) target T cell inhibitory pathways that are responsible for cancer tolerance by down-modulating immune functions. ICI have revolutionized patients care with lung cancer. Nevertheless, restoring endogenous antitumor T-cell responses can induce immune related adverse events, such as sarcoidosis. We report here the first case of a thoracic and cutaneous sarcoid-like reaction in a patient with a relapsing unresectable non-small cell lung cancer (NSCLC) treated with nivolumab, an anti-PD-1 mAb. The expression of PD-1 and its ligands, PD-L1 and PD-L2, was assessed by flow cytometry on peripheral blood mononuclear cells (PBMC) and compared to patients who had discontinued nivolumab therapy without having developed any immune related adverse events. PD-L1 expression was transiently increased on B cells, T cells and monocytes, whereas PD-L2 expression was not modulated. PD-1 was transiently undetectable when PD-L1 was maximal, before returning to basal level. Sarcoidosis spontaneously resolved, without corticotherapy. This case sheds the light on a complex regulation of PD-L1 expression in vivo on PBMC after nivolumab arrest and triggers the question of monitoring the expression of immune checkpoint on immune cells during and after treatment with ICI.
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      name:Simon Blanchard
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            name:Université de Nantes, Université d’Angers
            address:
               name:CRCINA, INSERM, Université de Nantes, Université d’Angers, Angers, France
               type:PostalAddress
            type:Organization
            name:LabEx ImmunoGraftOnco
            address:
               name:LabEx ImmunoGraftOnco, Angers-Nantes, France
               type:PostalAddress
            type:Organization
            name:Centre Hospitalier Universitaire
            address:
               name:Laboratoire d’Immunologie et Allergologie, Centre Hospitalier Universitaire, Angers, France
               type:PostalAddress
            type:Organization
      name:Thierry Urban
      affiliation:
            name:Centre Hospitalier Universitaire
            address:
               name:Service de Pneumologie, Centre Hospitalier Universitaire, Angers, France
               type:PostalAddress
            type:Organization
            name:Université d’Angers, UMR INSERM 1066 CNRS 6021
            address:
               name:MINT, Université d’Angers, UMR INSERM 1066 CNRS 6021, Angers, France
               type:PostalAddress
            type:Organization
      name:Anne Croué
      affiliation:
            name:Laboratoire d’Histopathologie-Cytopathologie, Centre Hospitalier Universitaire
            address:
               name:Département de Pathologie Cellulaire et Tissulaire, Laboratoire d’Histopathologie-Cytopathologie, Centre Hospitalier Universitaire, Angers, France
               type:PostalAddress
            type:Organization
      name:Marie-Christine Rousselet
      affiliation:
            name:Laboratoire d’Histopathologie-Cytopathologie, Centre Hospitalier Universitaire
            address:
               name:Département de Pathologie Cellulaire et Tissulaire, Laboratoire d’Histopathologie-Cytopathologie, Centre Hospitalier Universitaire, Angers, France
               type:PostalAddress
            type:Organization
      name:Sarah Le Roux
      affiliation:
            name:Laboratoire d’Histopathologie-Cytopathologie, Centre Hospitalier Universitaire
            address:
               name:Département de Pathologie Cellulaire et Tissulaire, Laboratoire d’Histopathologie-Cytopathologie, Centre Hospitalier Universitaire, Angers, France
               type:PostalAddress
            type:Organization
      name:Nathalie Labarrière
      affiliation:
            name:LabEx ImmunoGraftOnco
            address:
               name:LabEx ImmunoGraftOnco, Angers-Nantes, France
               type:PostalAddress
            type:Organization
            name:Université d’Angers, Université de Nantes
            address:
               name:CRCINA, INSERM, Université d’Angers, Université de Nantes, Nantes, France
               type:PostalAddress
            type:Organization
      name:Pascale Jeannin
      affiliation:
            name:Université de Nantes, Université d’Angers
            address:
               name:CRCINA, INSERM, Université de Nantes, Université d’Angers, Angers, France
               type:PostalAddress
            type:Organization
            name:LabEx ImmunoGraftOnco
            address:
               name:LabEx ImmunoGraftOnco, Angers-Nantes, France
               type:PostalAddress
            type:Organization
            name:Centre Hospitalier Universitaire
            address:
               name:Laboratoire d’Immunologie et Allergologie, Centre Hospitalier Universitaire, Angers, France
               type:PostalAddress
            type:Organization
      name:José Hureaux
      url:http://orcid.org/0000-0002-3941-3860
      affiliation:
            name:Centre Hospitalier Universitaire
            address:
               name:Service de Pneumologie, Centre Hospitalier Universitaire, Angers, France
               type:PostalAddress
            type:Organization
            name:Université d’Angers, UMR INSERM 1066 CNRS 6021
            address:
               name:MINT, Université d’Angers, UMR INSERM 1066 CNRS 6021, Angers, France
               type:PostalAddress
            type:Organization
      email:[email protected]
PostalAddress:
      name:CRCINA, INSERM, Université de Nantes, Université d’Angers, Angers, France
      name:LabEx ImmunoGraftOnco, Angers-Nantes, France
      name:CRCINA, INSERM, Université de Nantes, Université d’Angers, Angers, France
      name:LabEx ImmunoGraftOnco, Angers-Nantes, France
      name:Laboratoire d’Immunologie et Allergologie, Centre Hospitalier Universitaire, Angers, France
      name:CRCINA, INSERM, Université de Nantes, Université d’Angers, Angers, France
      name:LabEx ImmunoGraftOnco, Angers-Nantes, France
      name:Laboratoire d’Immunologie et Allergologie, Centre Hospitalier Universitaire, Angers, France
      name:Service de Pneumologie, Centre Hospitalier Universitaire, Angers, France
      name:MINT, Université d’Angers, UMR INSERM 1066 CNRS 6021, Angers, France
      name:Département de Pathologie Cellulaire et Tissulaire, Laboratoire d’Histopathologie-Cytopathologie, Centre Hospitalier Universitaire, Angers, France
      name:Département de Pathologie Cellulaire et Tissulaire, Laboratoire d’Histopathologie-Cytopathologie, Centre Hospitalier Universitaire, Angers, France
      name:Département de Pathologie Cellulaire et Tissulaire, Laboratoire d’Histopathologie-Cytopathologie, Centre Hospitalier Universitaire, Angers, France
      name:LabEx ImmunoGraftOnco, Angers-Nantes, France
      name:CRCINA, INSERM, Université d’Angers, Université de Nantes, Nantes, France
      name:CRCINA, INSERM, Université de Nantes, Université d’Angers, Angers, France
      name:LabEx ImmunoGraftOnco, Angers-Nantes, France
      name:Laboratoire d’Immunologie et Allergologie, Centre Hospitalier Universitaire, Angers, France
      name:Service de Pneumologie, Centre Hospitalier Universitaire, Angers, France
      name:MINT, Université d’Angers, UMR INSERM 1066 CNRS 6021, Angers, France

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