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Microarray gene expression analysis to evaluate cell type specific expression of targets relevant for immunotherapy of hematological malignancies

Pont, MJ and Honders, MW and Kremer, AN and Van Kooten, C and Out, C and Hiemstra, PS and De Boer, HC and Jager, MJ and Schmelzer, E and Vries, RG and Al Hinai, AS and Kroes, WG and Monajemi, R and Goeman, JJ and Böhringer, S and Marijt, WAF and Falkenburg, JHF and Griffioen, M (2016) Microarray gene expression analysis to evaluate cell type specific expression of targets relevant for immunotherapy of hematological malignancies. PLoS ONE, 11 (5).

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Abstract

Cellular immunotherapy has proven to be effective in the treatment of hematological cancers by donor lymphocyte infusion after allogeneic hematopoietic stem cell transplantation and more recently by targeted therapy with chimeric antigen or T-cell receptor-engineered T cells. However, dependent on the tissue distribution of the antigens that are targeted, anti-tumor responses can be accompanied by undesired side effects. Therefore, detailed tissue distribution analysis is essential to estimate potential efficacy and toxicity of candidate targets for immunotherapy of hematological malignancies. We performed microarray gene expression analysis of hematological malignancies of different origins, healthy hematopoietic cells and various non-hematopoietic cell types from organs that are often targeted in detrimental immune responses after allogeneic stem cell transplantation leading to graft-versus-host disease. Non-hematopoietic cells were also cultured in the presence of IFN-γ to analyze gene expression under inflammatory circumstances. Gene expression was investigated by Illumina HT12.0 microarrays and quality control analysis was performed to confirm the cell-type origin and exclude contamination of non-hematopoietic cell samples with peripheral blood cells. Microarray data were validated by quantitative RT-PCR showing strong correlations between both platforms. Detailed gene expression profiles were generated for various minor histocompatibility antigens and B-cell surface antigens to illustrate the value of the microarray dataset to estimate efficacy and toxicity of candidate targets for immunotherapy. In conclusion, our microarray database provides a relevant platform to analyze and select candidate antigens with hematopoietic (lineage)-restricted expression as potential targets for immunotherapy of hematological cancers.

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Details

Item Type: Article
Status: Published
Creators/Authors:
CreatorsEmailPitt UsernameORCID
Pont, MJ
Honders, MW
Kremer, AN
Van Kooten, C
Out, C
Hiemstra, PS
De Boer, HC
Jager, MJ
Schmelzer, Eevs14@pitt.eduEVS14
Vries, RG
Al Hinai, AS
Kroes, WG
Monajemi, R
Goeman, JJ
Böhringer, S
Marijt, WAF
Falkenburg, JHF
Griffioen, M
Contributors:
ContributionContributors NameEmailPitt UsernameORCID
EditorSt-Pierre, YvesUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Centers: Other Centers, Institutes, Offices, or Units > McGowan Institute for Regenerative Medicine
Date: 1 May 2016
Date Type: Publication
Access Restriction: No restriction; Release the ETD for access worldwide immediately.
Journal or Publication Title: PLoS ONE
Volume: 11
Number: 5
DOI or Unique Handle: 10.1371/journal.pone.0155165
Institution: University of Pittsburgh
Refereed: Yes
Date Deposited: 31 Aug 2016 18:05
Last Modified: 30 Mar 2021 10:55
URI: http://d-scholarship.pitt.edu/id/eprint/28235

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