title: Expression of PD-1 (CD279) and FoxP3 in diffuse large B-cell lymphoma.
abstract: The role of the microenvironment in high-grade lymphoma is not well defined. In this report, we employ immunohistochemistry to characterise programmed death-1 (PD-1/CD279) and FoxP3 expression in 70 cases of diffuse large B-cell lymphoma (DLBCL). PD-1 is a surface marker characteristic of follicular helper T-cells whilst FoxP3 is characteristic of Tregs. We demonstrate variable infiltration with CD4(+) T-cells (<10 to >50 % of all lymph node cells) and PD-1(hi) cells (0.1 to 1.5 % of all cells). CD4(+) T-cells can be distributed in clusters or more diffusely and PD-1(hi) cells, but not FoxP3(+) cells, are found in rosettes around lymphoma cells. Cases with high CD4(+) T-cell numbers tended to have higher numbers of both PD-1(hi) and FoxP3(+) cells. Cases with total CD4(+) T-cell, PD-1(hi) and FoxP3(+) numbers above the median associate with better clinical outcome. Overall, we demonstrate that infiltration by CD4(+) T-cells, including both FoxP3(+) and PD-1(hi) subsets, correlates with prognosis in DLBCL. In distinction to previous reported series, patients (91 %) were treated with rituximab-containing regimens, suggesting that the effects of CD4+ T-cell infiltration are maintained in the rituximab era. This work suggests that determinants of total CD4(+) T-cell infiltration, either molecular characteristics of the lymphoma or the patients' immune system, and not individual T-cell subsets, correlate with clinical outcome.
authors.affiliation: Department of Cancer Studies and Molecular Medicine, Ernest and Helen Scott Haematology Research Institute and MRC Toxicology Unit, University of Leicester, Lancaster Road, Leicester, LE1 9HN, UK.
authors.forename: Matthew J
authors.initials: MJ
authors.lastname: Ahearne
authors.forename: Kaljit
authors.initials: K
authors.lastname: Bhuller
authors.forename: Roger
authors.initials: R
authors.lastname: Hew
authors.forename: Hazem
authors.initials: H
authors.lastname: Ibrahim
authors.forename: Kikkeri
authors.initials: K
authors.lastname: Naresh
authors.forename: Simon D
authors.initials: SD
authors.lastname: Wagner
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D005260:Female; D051858:Forkhead Transcription Factors / Q000032:analysis*; D006801:Humans; D060889:Inducible T-Cell Co-Stimulator Protein / Q000032:analysis; D007770:L-Lactate Dehydrogenase / Q000032:analysis; D016403:Lymphoma, Large B-Cell, Diffuse / Q000276:immunology*; D008297:Male; D008875:Middle Aged; D061026:Programmed Cell Death 1 Receptor / Q000032:analysis*; D054380:Receptors, CXCR5 / Q000032:analysis
chemical_list: C095085:CXCR5 protein, human; C418974:FOXP3 protein, human; D051858:Forkhead Transcription Factors; C556692:ICOS protein, human; D060889:Inducible T-Cell Co-Stimulator Protein; C105992:PDCD1 protein, human; D061026:Programmed Cell Death 1 Receptor; D054380:Receptors, CXCR5; D007770:L-Lactate Dehydrogenase