PD-1 Expression in Chronic Lymphocytic Leukemia/Small Lymphocytic Lymphoma (CLL/SLL) and Large B-cell Richter Transformation (DLBCL-RT)
- 1 July 2018
- journal article
- research article
- Published by Ovid Technologies (Wolters Kluwer Health) in The American Journal of Surgical Pathology
- Vol. 42 (7), 843-854
- https://doi.org/10.1097/pas.0000000000001077
Abstract
Chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL) is a low-grade B-cell neoplasm and ∼2% to 9% patients develop an aggressive lymphoma, most commonly diffuse large B-cell lymphoma (Richter transformation, DLBCL-RT). Programmed death-1 (PD-1) pathway plays a crucial role in tumor host immunity evasion and its blockade has emerged as an effective anti-cancer immunotherapy. PD-L1 and PD-1 expression has shown predictive value in anti-PD cancer immunotherapy; however, it has not been well documented in CLL/SLL and DLBCL-RT. We evaluated PD-1 and PD-L1 expression by immunohistochemistry in 39 CLL/SLL, 15 DLBCL-RT, and 26 other DLBCL. In CLL/SLL, neoplastic B-cell PD-1 expression was weak and restricted to prolymphocytes/paraimmunoblasts within proliferation centers (PCs) and accentuated PCs of all sizes. Neoplastic B-cell PD-1 expression was highly prevalent and demonstrated increased intensity in DLBCL-RT, but in contrast was only rarely seen in other DLBCL (12/15 vs. 1/26; PP>0.05) as well as background histiocytes and dendritic cells. Overall survival of DLBCL-RT was significantly inferior to that of the other DLBCL (median, 16.9 vs. 106.1 mo; P=0.002). Our findings suggest a biological continuum from prolymphocytes/paraimmunoblasts in CLL/SLL PCs to the neoplastic B-cells in DLBCL-RT. The characteristic PD-1 expression in DLBCL-RT makes it a potential surrogate marker for determining clonal relatedness to CLL/SLL, which may have important prognostic and therapeutic implications.Keywords
This publication has 62 references indexed in Scilit:
- Diffuse large B‐cell lymphoma (Richter syndrome) in patients with chronic lymphocytic leukaemia (CLL): a cohort study of newly diagnosed patientsBritish Journal of Haematology, 2013
- The PD-1/PD-L1 axis contributes to T-cell dysfunction in chronic lymphocytic leukemiaHaematologica, 2013
- Safety, Activity, and Immune Correlates of Anti–PD-1 Antibody in CancerNew England Journal of Medicine, 2012
- Programmed Death-1 and Its Ligand Are Novel Immunotolerant Molecules Expressed on Leukemic B Cells in Chronic Lymphocytic LeukemiaPLOS ONE, 2012
- Constitutive AP-1 Activity and EBV Infection Induce PD-L1 in Hodgkin Lymphomas and Posttransplant Lymphoproliferative Disorders: Implications for Targeted TherapyClinical Cancer Research, 2012
- Surface IgM stimulation induces MEK1/2-dependent MYC expression in chronic lymphocytic leukemia cellsBlood, 2012
- The PD‐1 pathway in tolerance and autoimmunityImmunological Reviews, 2010
- Expanded and highly active proliferation centers identify a histological subtype of chronic lymphocytic leukemia ("accelerated" chronic lymphocytic leukemia) with aggressive clinical behaviorHaematologica, 2010
- Chronic lymphocytic leukemia T cells show impaired immunological synapse formation that can be reversed with an immunomodulating drugJCI Insight, 2008
- Programmed Death-1 (PD-1) is a Marker of Germinal Center-associated T Cells and Angioimmunoblastic T-Cell LymphomaThe American Journal of Surgical Pathology, 2006