PD-1/PD-L1 expression and interaction by automated quantitative immunofluorescent analysis show adverse prognostic impact in patients with diffuse large B-cell lymphoma having T-cell infiltration: a study from the International DLBCL Consortium Program.
dc.contributor.author | Li, Ling | |
dc.contributor.author | Sun, Ruifang | |
dc.contributor.author | Miao, Yi | |
dc.contributor.author | Tran, Thai | |
dc.contributor.author | Adams, Lisa | |
dc.contributor.author | Roscoe, Nathan | |
dc.contributor.author | Xu, Bing | |
dc.contributor.author | Manyam, Ganiraju C | |
dc.contributor.author | Tan, Xiaohong | |
dc.contributor.author | Zhang, Hongwei | |
dc.contributor.author | Xiao, Min | |
dc.contributor.author | Tzankov, Alexandar | |
dc.contributor.author | Visco, Carlo | |
dc.contributor.author | Dybkaer, Karen | |
dc.contributor.author | Bhagat, Govind | |
dc.contributor.author | Tam, Wayne | |
dc.contributor.author | Hsi, Eric D | |
dc.contributor.author | van Krieken, J Han | |
dc.contributor.author | You, Hua | |
dc.contributor.author | Huh, Jooryung | |
dc.contributor.author | Ponzoni, Maurilio | |
dc.contributor.author | Ferreri, Andrés JM | |
dc.contributor.author | Møller, Michael B | |
dc.contributor.author | Piris, Miguel A | |
dc.contributor.author | Zhang, Mingzhi | |
dc.contributor.author | Winter, Jane N | |
dc.contributor.author | Medeiros, L Jeffrey | |
dc.contributor.author | Rassidakis, George Z | |
dc.contributor.author | Vaupel, Christine A | |
dc.contributor.author | Li, Yong | |
dc.contributor.author | Dakappagari, Naveen | |
dc.contributor.author | Xu-Monette, Zijun Y | |
dc.contributor.author | Young, Ken H | |
dc.date.accessioned | 2019-09-21T21:26:42Z | |
dc.date.available | 2019-09-21T21:26:42Z | |
dc.date.issued | 2019-06 | |
dc.date.updated | 2019-09-21T21:26:41Z | |
dc.description.abstract | Programmed cell death protein 1/programmed cell death protein ligand1 (PD-1/PD-L1) interaction is an important immune checkpoint targeted by anti-PD-1/PD-L1 immunotherapies. However, the observed prognostic significance of PD-1/PD-L1 expression in diffuse large B-cell lymphoma treated with the standard of care has been inconsistent and even contradictory. To clarify the prognostic role of PD-1/PD-L1 expression and interaction in diffuse large B-cell lymphoma, in this study we used 3-marker fluorescent multiplex immunohistochemistry and Automated Quantitative Analysis Technology to assess the CD3+, PD-L1+, and PD-1+CD3+ expression in diagnostic samples and PD-1/PD-L1 interaction as indicated by presence of PD-1+CD3+ cells in the vicinity of PD-L1+ cells, analyzed their prognostic effects in 414 patients with de novo diffuse large B-cell lymphoma, and examined whether PD-1/PD-L1 interaction is required for the prognostic role of PD-1+/PD-L1+ expression. We found that low T-cell tissue cellularity, tissue PD-L1+ expression (irrespective of cell types), PD-1+CD3+ expression, and PD-1/PD-L1 interaction showed hierarchical adverse prognostic effects in the study cohort. PD-1/PD-L1 interaction showed higher sensitivity and specificity than PD-1+ and PD-L1+ expression in predicting inferior prognosis in patients with high CD3+ tissue cellularity ("hot"/inflammatory tumors). However, both PD-1+ and PD-L1+ expression showed adverse prognostic effects independent of PD-1/PD-L1 interaction, and PD-1/PD-L1 interaction showed favorable prognostic effect in PD-L1+ patients without high CD3+ tissue cellularity. Macrophage function and tumor-cell MYC expression may contribute to the PD-1-independent adverse prognostic effect of PD-L1+ expression. In summary, low T-cell tissue cellularity has unfavorable prognostic impact in diffuse large B-cell lymphoma, and tissue PD-L1+ expression and T-cell-derived PD-1+ expression have significant adverse impact only in patients with high T-cell infiltration. PD-1/PD-L1 interaction in tissue is essential but not always responsible for the inhibitory effect of PD-L1+/PD-1+ expression. These results suggest the benefit of PD-1/PD-L1 blockade therapies only in patients with sufficient T-cell infiltration, and the potential of immunofluorescent assays and Automated Quantitative Analysis in the clinical assessment of PD-1/PD-L1 expression and interaction. | |
dc.identifier | 10.1038/s41379-018-0193-5 | |
dc.identifier.issn | 0893-3952 | |
dc.identifier.issn | 1530-0285 | |
dc.identifier.uri | ||
dc.language | eng | |
dc.publisher | Elsevier BV | |
dc.relation.ispartof | Modern pathology : an official journal of the United States and Canadian Academy of Pathology, Inc | |
dc.relation.isversionof | 10.1038/s41379-018-0193-5 | |
dc.subject | Science & Technology | |
dc.subject | Life Sciences & Biomedicine | |
dc.subject | Pathology | |
dc.subject | DEATH-LIGAND 1 | |
dc.subject | PD-1 BLOCKADE | |
dc.subject | RITUXIMAB | |
dc.subject | SURVIVAL | |
dc.subject | HODGKIN | |
dc.subject | PHAGOCYTOSIS | |
dc.subject | MACROPHAGES | |
dc.subject | ENGAGEMENT | |
dc.subject | CANCER | |
dc.subject | MEMBER | |
dc.title | PD-1/PD-L1 expression and interaction by automated quantitative immunofluorescent analysis show adverse prognostic impact in patients with diffuse large B-cell lymphoma having T-cell infiltration: a study from the International DLBCL Consortium Program. | |
dc.type | Journal article | |
duke.contributor.orcid | Xu-Monette, Zijun Y|0000-0002-7615-3949 | |
duke.contributor.orcid | Young, Ken H|0000-0002-5755-8932 | |
pubs.begin-page | 741 | |
pubs.end-page | 754 | |
pubs.issue | 6 | |
pubs.organisational-group | School of Medicine | |
pubs.organisational-group | Duke | |
pubs.organisational-group | Pathology | |
pubs.organisational-group | Clinical Science Departments | |
pubs.publication-status | Published | |
pubs.volume | 32 |
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