Mechanisms of PD-1/PD-L1 expression and prognostic relevance in non-Hodgkin lymphoma: a summary of immunohistochemical studies

Pauline Gravelle, Barbara Burroni, Sarah Péricart, Cédric Rossi, Christine Bezombes, Marie Tosolini, Diane Damotte, Pierre Brousset, Jean-Jacques Fournié and Camille Laurent _

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Oncotarget. 2017; 8:44960-44975. https://doi.org/10.18632/oncotarget.16680

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Pauline Gravelle1,2,3,4,5,6,10, Barbara Burroni7, Sarah Péricart1,2,3,4,5,6,10, Cédric Rossi2,3,4,5,6,8,10, Christine Bezombes2,3,4,5,6,10, Marie Tosolini2,3,4,5,6,10, Diane Damotte7,9, Pierre Brousset1,2,3,4,5,6,10, Jean-Jacques Fournié3,4,5,6,10 and Camille Laurent1,2,3,4,5,6,10

1 Département de Pathologie, CHU Toulouse, Institut Universitaire du Cancer de Toulouse, Centre Hospitalo-Universitaire de Toulouse, Toulouse, France

2 Institut Universitaire du Cancer de Toulouse, Toulouse, France

3 Centre de Recherches en Cancérologie de Toulouse, UMR1037 INSERM-Université Toulouse III, Toulouse, France

4 Laboratoire d’Excellence TOUCAN, Toulouse, France

5 Programme Hospitalo-Universitaire en Cancérologie CAPTOR, Toulouse, France

6 Institut Carnot CALYM, Toulouse, France

7 Service de Pathologie Hôpitaux Universitaires Paris Centre, Hopital Cochin, Paris, France

8 CHU le Bocage, Hématologie Clinique, Dijon, France

9 Centre de Recherche des Cordeliers, INSERM U1138, Paris, France

10 Paul-Sabatier, ERL 5294 CNRS, Université de Toulouse, Toulouse, France

Correspondence to:

Camille Laurent, email:

Keywords: PD-1/PD-L1 expression; non-Hodgkin lymphoma; prognostic value

Received: November 14, 2016 Accepted: March 16, 2017 Published: March 29, 2017


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.

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