TY - JOUR
T1 - Graft-versus-host disease–free antitumoral signature after allogeneic donor lymphocyte injection identified by proteomics and systems biology
AU - Liu, Xiaowen
AU - Yue, Zongliang
AU - Cao, Yimou
AU - Taylor, Lauren
AU - Zhang, Qing
AU - Choi, Sung W.
AU - Hanash, Samir
AU - Ito, Sawa
AU - Chen, Jake Y.
AU - Wu, Huanmei
AU - Paczesny, Sophie
N1 - Publisher Copyright:
Copyright © 2019 American Society of Clinical Oncology. All rights reserved.
PY - 2019
Y1 - 2019
N2 - PURPOSE As a tumor immunotherapy, allogeneic hematopoietic cell transplantation with subsequent donor lymphocyte injection (DLI) aims to induce the graft-versus-tumor (GVT) effect but often also leads to acute graft-versus-host disease (GVHD). Plasma tests that can predict the likelihood of GVT without GVHD are still needed. PATIENTS AND METHODS We first used an intact-protein analysis system to profile the plasma proteome post-DLI of patients who experienced GVT and acute GVHD for comparison with the proteome of patients who experienced GVT without GVHD in a training set. Our novel six-step systems biology analysis involved removing common proteins and GVHD-specific proteins, creating a protein-protein interaction network, calculating relevance and penalty scores, and visualizing candidate biomarkers in gene networks. We then performed a second proteomics experiment in a validation set of patients who experienced GVT without acute GVHD after DLI for comparison with the proteome of patients before DLI. We next combined the two experiments to define a biologically relevant signature of GVT without GVHD. An independent experiment with single-cell profiling in tumor antigen–activated T cells from a patient with post–hematopoietic cell transplantation relapse was performed. RESULTS The approach provided a list of 46 proteins in the training set, and 30 proteins in the validation set were associated with GVT without GVHD. The combination of the two experiments defined a unique 61-protein signature of GVT without GVHD. Finally, the single-cell profiling in activated T cells found 43 of the 61 genes. Novel markers, such as RPL23, ILF2, CD58, and CRTAM, were identified and could be extended to other antitumoral responses. CONCLUSION Our multiomic analysis provides, to our knowledge, the first human plasma signature for GVT without GVHD. Risk stratification on the basis of this signature would allow for customized treatment plans.
AB - PURPOSE As a tumor immunotherapy, allogeneic hematopoietic cell transplantation with subsequent donor lymphocyte injection (DLI) aims to induce the graft-versus-tumor (GVT) effect but often also leads to acute graft-versus-host disease (GVHD). Plasma tests that can predict the likelihood of GVT without GVHD are still needed. PATIENTS AND METHODS We first used an intact-protein analysis system to profile the plasma proteome post-DLI of patients who experienced GVT and acute GVHD for comparison with the proteome of patients who experienced GVT without GVHD in a training set. Our novel six-step systems biology analysis involved removing common proteins and GVHD-specific proteins, creating a protein-protein interaction network, calculating relevance and penalty scores, and visualizing candidate biomarkers in gene networks. We then performed a second proteomics experiment in a validation set of patients who experienced GVT without acute GVHD after DLI for comparison with the proteome of patients before DLI. We next combined the two experiments to define a biologically relevant signature of GVT without GVHD. An independent experiment with single-cell profiling in tumor antigen–activated T cells from a patient with post–hematopoietic cell transplantation relapse was performed. RESULTS The approach provided a list of 46 proteins in the training set, and 30 proteins in the validation set were associated with GVT without GVHD. The combination of the two experiments defined a unique 61-protein signature of GVT without GVHD. Finally, the single-cell profiling in activated T cells found 43 of the 61 genes. Novel markers, such as RPL23, ILF2, CD58, and CRTAM, were identified and could be extended to other antitumoral responses. CONCLUSION Our multiomic analysis provides, to our knowledge, the first human plasma signature for GVT without GVHD. Risk stratification on the basis of this signature would allow for customized treatment plans.
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U2 - 10.1200/PO.18.00365
DO - 10.1200/PO.18.00365
M3 - Article
C2 - 31406955
AN - SCOPUS:85077484743
SN - 2473-4284
VL - 3
SP - 1
EP - 11
JO - JCO Precision Oncology
JF - JCO Precision Oncology
ER -