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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.

Publication ,  Journal Article
Li, L; Sun, R; Miao, Y; Tran, T; Adams, L; Roscoe, N; Xu, B; Manyam, GC; Tan, X; Zhang, H; Xiao, M; Tzankov, A; Visco, C; Dybkaer, K; Li, Y ...
Published in: Mod Pathol
June 2019

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.

Duke Scholars

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Published In

Mod Pathol

DOI

EISSN

1530-0285

Publication Date

June 2019

Volume

32

Issue

6

Start / End Page

741 / 754

Location

United States

Related Subject Headings

  • Tumor Microenvironment
  • T-Lymphocytes
  • Programmed Cell Death 1 Receptor
  • Prognosis
  • Pathology
  • Middle Aged
  • Male
  • Lymphoma, Large B-Cell, Diffuse
  • Lymphocytes, Tumor-Infiltrating
  • Humans
 

Citation

APA
Chicago
ICMJE
MLA
NLM
Li, Ling, Ruifang Sun, Yi Miao, Thai Tran, Lisa Adams, Nathan Roscoe, Bing Xu, et al. “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.Mod Pathol 32, no. 6 (June 2019): 741–54. https://doi.org/10.1038/s41379-018-0193-5.
Li L, Sun R, Miao Y, Tran T, Adams L, Roscoe N, Xu B, Manyam GC, Tan X, Zhang H, Xiao M, Tzankov A, Visco C, Dybkaer K, Bhagat G, Tam W, Hsi ED, van Krieken JH, You H, Huh J, Ponzoni M, Ferreri AJM, Møller MB, Piris MA, Zhang M, Winter JN, Medeiros LJ, Rassidakis GZ, Vaupel CA, Li Y, Dakappagari N, Xu-Monette ZY, Young KH. 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. Mod Pathol. 2019 Jun;32(6):741–754.

Published In

Mod Pathol

DOI

EISSN

1530-0285

Publication Date

June 2019

Volume

32

Issue

6

Start / End Page

741 / 754

Location

United States

Related Subject Headings

  • Tumor Microenvironment
  • T-Lymphocytes
  • Programmed Cell Death 1 Receptor
  • Prognosis
  • Pathology
  • Middle Aged
  • Male
  • Lymphoma, Large B-Cell, Diffuse
  • Lymphocytes, Tumor-Infiltrating
  • Humans