title: Mechanisms of PD-1/PD-L1 expression and prognostic relevance in non-Hodgkin lymphoma: a summary of immunohistochemical studies.
abstract: Immune checkpoint blockade therapeutics, notably antibodies targeting the programmed death 1 (PD-1) receptor and its PD-L1 and PD-L2 ligands, are currently revolutionizing the treatment of cancer. For a sizeable fraction of patients with melanoma, lung, kidney and several other solid cancers, monoclonal antibodies that neutralize the interactions of the PD-1/PD-L1 complex allow the reconstitution of long-lasting antitumor immunity. In hematological malignancies this novel therapeutic strategy is far less documented, although promising clinical responses have been seen in refractory and relapsed Hodgkin lymphoma patients. This review describes our current knowledge of PD-1 and PD-L1 expression, as reported by immunohistochemical staining in both non-Hodgkin lymphoma cells and their surrounding immune cells. Here, we discuss the multiple intrinsic and extrinsic mechanisms by which both T and B cell lymphomas up-regulate the PD-1/PD-L1 axis, and review current knowledge about the prognostic significance of its immunohistochemical detection. This body of literature establishes the cell surface expression of PD-1/PD-L1 as a critical determinant for the identification of non-Hodgkin lymphoma patients eligible for immune checkpoint blockade therapies.
authors.affiliation: Département de Pathologie, CHU Toulouse, Institut Universitaire du Cancer de Toulouse, Centre Hospitalo-Universitaire de Toulouse, Toulouse, France.|Institut Universitaire du Cancer de Toulouse, Toulouse, France.|Centre de Recherches en Cancérologie de Toulouse, UMR1037 INSERM-Université Toulouse III, Toulouse, France.|Laboratoire d'Excellence TOUCAN, Toulouse, France.|Programme Hospitalo-Universitaire en Cancérologie CAPTOR, Toulouse, France.|Institut Carnot CALYM, Toulouse, France.|Paul-Sabatier, ERL 5294 CNRS, Université de Toulouse, Toulouse, France.
authors.forename: Pauline
authors.initials: P
authors.lastname: Gravelle
authors.affiliation: Service de Pathologie Hôpitaux Universitaires Paris Centre, Hopital Cochin, Paris, France.
authors.forename: Barbara
authors.initials: B
authors.lastname: Burroni
authors.affiliation: Département de Pathologie, CHU Toulouse, Institut Universitaire du Cancer de Toulouse, Centre Hospitalo-Universitaire de Toulouse, Toulouse, France.|Institut Universitaire du Cancer de Toulouse, Toulouse, France.|Centre de Recherches en Cancérologie de Toulouse, UMR1037 INSERM-Université Toulouse III, Toulouse, France.|Laboratoire d'Excellence TOUCAN, Toulouse, France.|Programme Hospitalo-Universitaire en Cancérologie CAPTOR, Toulouse, France.|Institut Carnot CALYM, Toulouse, France.|Paul-Sabatier, ERL 5294 CNRS, Université de Toulouse, Toulouse, France.
authors.forename: Sarah
authors.initials: S
authors.lastname: Péricart
authors.affiliation: Institut Universitaire du Cancer de Toulouse, Toulouse, France.|Centre de Recherches en Cancérologie de Toulouse, UMR1037 INSERM-Université Toulouse III, Toulouse, France.|Laboratoire d'Excellence TOUCAN, Toulouse, France.|Programme Hospitalo-Universitaire en Cancérologie CAPTOR, Toulouse, France.|Institut Carnot CALYM, Toulouse, France.|CHU le Bocage, Hématologie Clinique, Dijon, France.|Paul-Sabatier, ERL 5294 CNRS, Université de Toulouse, Toulouse, France.
authors.forename: Cédric
authors.initials: C
authors.lastname: Rossi
authors.affiliation: Institut Universitaire du Cancer de Toulouse, Toulouse, France.|Centre de Recherches en Cancérologie de Toulouse, UMR1037 INSERM-Université Toulouse III, Toulouse, France.|Laboratoire d'Excellence TOUCAN, Toulouse, France.|Programme Hospitalo-Universitaire en Cancérologie CAPTOR, Toulouse, France.|Institut Carnot CALYM, Toulouse, France.|Paul-Sabatier, ERL 5294 CNRS, Université de Toulouse, Toulouse, France.
authors.forename: Christine
authors.initials: C
authors.lastname: Bezombes
authors.affiliation: Institut Universitaire du Cancer de Toulouse, Toulouse, France.|Centre de Recherches en Cancérologie de Toulouse, UMR1037 INSERM-Université Toulouse III, Toulouse, France.|Laboratoire d'Excellence TOUCAN, Toulouse, France.|Programme Hospitalo-Universitaire en Cancérologie CAPTOR, Toulouse, France.|Institut Carnot CALYM, Toulouse, France.|Paul-Sabatier, ERL 5294 CNRS, Université de Toulouse, Toulouse, France.
authors.forename: Marie
authors.initials: M
authors.lastname: Tosolini
authors.affiliation: Service de Pathologie Hôpitaux Universitaires Paris Centre, Hopital Cochin, Paris, France.|Centre de Recherche des Cordeliers, INSERM U1138, Paris, France.
authors.forename: Diane
authors.initials: D
authors.lastname: Damotte
authors.affiliation: Département de Pathologie, CHU Toulouse, Institut Universitaire du Cancer de Toulouse, Centre Hospitalo-Universitaire de Toulouse, Toulouse, France.|Institut Universitaire du Cancer de Toulouse, Toulouse, France.|Centre de Recherches en Cancérologie de Toulouse, UMR1037 INSERM-Université Toulouse III, Toulouse, France.|Laboratoire d'Excellence TOUCAN, Toulouse, France.|Programme Hospitalo-Universitaire en Cancérologie CAPTOR, Toulouse, France.|Institut Carnot CALYM, Toulouse, France.|Paul-Sabatier, ERL 5294 CNRS, Université de Toulouse, Toulouse, France.
authors.forename: Pierre
authors.initials: P
authors.lastname: Brousset
authors.affiliation: Centre de Recherches en Cancérologie de Toulouse, UMR1037 INSERM-Université Toulouse III, Toulouse, France.|Laboratoire d'Excellence TOUCAN, Toulouse, France.|Programme Hospitalo-Universitaire en Cancérologie CAPTOR, Toulouse, France.|Institut Carnot CALYM, Toulouse, France.|Paul-Sabatier, ERL 5294 CNRS, Université de Toulouse, Toulouse, France.
authors.forename: Jean-Jacques
authors.initials: JJ
authors.lastname: Fournié
authors.affiliation: Département de Pathologie, CHU Toulouse, Institut Universitaire du Cancer de Toulouse, Centre Hospitalo-Universitaire de Toulouse, Toulouse, France.|Institut Universitaire du Cancer de Toulouse, Toulouse, France.|Centre de Recherches en Cancérologie de Toulouse, UMR1037 INSERM-Université Toulouse III, Toulouse, France.|Laboratoire d'Excellence TOUCAN, Toulouse, France.|Programme Hospitalo-Universitaire en Cancérologie CAPTOR, Toulouse, France.|Institut Carnot CALYM, Toulouse, France.|Paul-Sabatier, ERL 5294 CNRS, Université de Toulouse, Toulouse, France.
authors.forename: Camille
authors.initials: C
authors.lastname: Laurent
mesh_terms: D000818:Animals; D060890:B7-H1 Antigen / Q000235:genetics / Q000378:metabolism*; D014408:Biomarkers, Tumor; D015870:Gene Expression; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D007150:Immunohistochemistry; D008228:Lymphoma, Non-Hodgkin / Q000175:diagnosis / Q000378:metabolism* / Q000401:mortality* / Q000628:therapy; D058990:Molecular Targeted Therapy; D011379:Prognosis; D061026:Programmed Cell Death 1 Receptor / Q000235:genetics / Q000378:metabolism*; D015398:Signal Transduction
chemical_list: D060890:B7-H1 Antigen; D014408:Biomarkers, Tumor; C423236:CD274 protein, human; D061026:Programmed Cell Death 1 Receptor
keywords: PD-1/PD-L1 expression; non-Hodgkin lymphoma; prognostic value