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Tumor derived exosome induction of the CD3+CD8+ T cell tolerogenic phenotype

Tumor derived exosome induction of the CD3+CD8+ T cell tolerogenic phenotype Maybruck and Gastman Journal for ImmunoTherapy of Cancer 2013, 1(Suppl 1):P165 http://www.immunotherapyofcancer.org/content/1/S1/P165 POSTER PRESENTATION Open Access Tumor derived exosome induction of the CD3 +CD8+ T cell tolerogenic phenotype Brian Maybruck , Brian Gastman From Society for Immunotherapy of Cancer 28th Annual Meeting National Harbor, MD, USA. 8-10 November 2013 Background were at the most 50% of the population. Congruent loss Traditionally, CD8+ T cells have been defined as being of CD27/28 expression was associated with an increased immunogenic; however, they have also been shown to ability to suppress responder T cell proliferation, indicat- demonstrate a tolerogenic phenotype. One area less ing immunosuppression. studied, regarding the tolerogenic phenotype of CD8+ T cells, is their role in cancer. What has been described is Conclusions that their suppressive phenotype is suggested to be This research has identified TD exosomes from multiple developed in the tumor microenvironment and can be cancer cell lines as a factor causing the CD3+CD8+ T correlated with the CD8+ T cells becoming CD27/28-. cell tolerogenic phenotype. Furthermore, the lack of What is unclear is the general mechanism that may trig- cell-to-cell contact needed between CD3+CD8+ T cells ger the tolerogenic development in CD8+ T cells. Via and the cancer cell lines to trigger this tolerogenic phe- multiple cancer cell lines, this research identified that notype implies that CD3+CD8+ T cell exposure to the tumor derived (TD) exosomes will cause the development tumor microenvironment may not be required for these of the tolerogenic phenotype in CD3+CD8+ T cells. cells to become suppressor cells. Current research is involved in the purification of the factor(s) from the TD Methods exosomes that may be causing this effect. Upon further Conditioned growth media from tumor cell lines were identification of this factor(s) it could be used to better processed by an exosome precipitation solution to purify understand the etiology of the dysfunction in immuno- exosomes. Confirmation of exosome isolation was based surveillance due to immunosubversion. upon the identification of 10 commonly found exosomal proteins from the purification. Human CD3+CD8+ T cells Published: 7 November 2013 were incubated with TD exosomes, tumor conditioned growth medium with and without exosomes, and exosome- free complete RPMI. Following this incubation, the CD3 doi:10.1186/2051-1426-1-S1-P165 +CD8+ T cells were analyzed for CD27/28 loss by flow Cite this article as: Maybruck and Gastman: Tumor derived exosome cytometry and suppression analysis (BrdU incorporation induction of the CD3+CD8+ T cell tolerogenic phenotype. Journal for ImmunoTherapy of Cancer 2013 1(Suppl 1):P165. assay) to examine for the tolerogenic T cell phenotype. Results The exosome-free complete RPMI control group and the tumor cell line conditioned growth medium without exo- some group, showed CD3+CD8+ T cell’sCD27/28 loss to be at most 12% of the population. In contrast, CD27/ 28 loss, when CD3+CD8+ T cells were incubated with tumor conditioned growth medium and TD exosomes, Immunology, Cleveland Clinic, Cleveland, OH, USA © 2013 Maybruck and Gastman; licensee BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. http://www.deepdyve.com/assets/images/DeepDyve-Logo-lg.png Journal for ImmunoTherapy of Cancer Springer Journals

Tumor derived exosome induction of the CD3+CD8+ T cell tolerogenic phenotype

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Publisher
Springer Journals
Copyright
Copyright © 2013 by Maybruck and Gastman; licensee BioMed Central Ltd.
Subject
Medicine & Public Health; Oncology
eISSN
2051-1426
DOI
10.1186/2051-1426-1-S1-P165
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Abstract

Maybruck and Gastman Journal for ImmunoTherapy of Cancer 2013, 1(Suppl 1):P165 http://www.immunotherapyofcancer.org/content/1/S1/P165 POSTER PRESENTATION Open Access Tumor derived exosome induction of the CD3 +CD8+ T cell tolerogenic phenotype Brian Maybruck , Brian Gastman From Society for Immunotherapy of Cancer 28th Annual Meeting National Harbor, MD, USA. 8-10 November 2013 Background were at the most 50% of the population. Congruent loss Traditionally, CD8+ T cells have been defined as being of CD27/28 expression was associated with an increased immunogenic; however, they have also been shown to ability to suppress responder T cell proliferation, indicat- demonstrate a tolerogenic phenotype. One area less ing immunosuppression. studied, regarding the tolerogenic phenotype of CD8+ T cells, is their role in cancer. What has been described is Conclusions that their suppressive phenotype is suggested to be This research has identified TD exosomes from multiple developed in the tumor microenvironment and can be cancer cell lines as a factor causing the CD3+CD8+ T correlated with the CD8+ T cells becoming CD27/28-. cell tolerogenic phenotype. Furthermore, the lack of What is unclear is the general mechanism that may trig- cell-to-cell contact needed between CD3+CD8+ T cells ger the tolerogenic development in CD8+ T cells. Via and the cancer cell lines to trigger this tolerogenic phe- multiple cancer cell lines, this research identified that notype implies that CD3+CD8+ T cell exposure to the tumor derived (TD) exosomes will cause the development tumor microenvironment may not be required for these of the tolerogenic phenotype in CD3+CD8+ T cells. cells to become suppressor cells. Current research is involved in the purification of the factor(s) from the TD Methods exosomes that may be causing this effect. Upon further Conditioned growth media from tumor cell lines were identification of this factor(s) it could be used to better processed by an exosome precipitation solution to purify understand the etiology of the dysfunction in immuno- exosomes. Confirmation of exosome isolation was based surveillance due to immunosubversion. upon the identification of 10 commonly found exosomal proteins from the purification. Human CD3+CD8+ T cells Published: 7 November 2013 were incubated with TD exosomes, tumor conditioned growth medium with and without exosomes, and exosome- free complete RPMI. Following this incubation, the CD3 doi:10.1186/2051-1426-1-S1-P165 +CD8+ T cells were analyzed for CD27/28 loss by flow Cite this article as: Maybruck and Gastman: Tumor derived exosome cytometry and suppression analysis (BrdU incorporation induction of the CD3+CD8+ T cell tolerogenic phenotype. Journal for ImmunoTherapy of Cancer 2013 1(Suppl 1):P165. assay) to examine for the tolerogenic T cell phenotype. Results The exosome-free complete RPMI control group and the tumor cell line conditioned growth medium without exo- some group, showed CD3+CD8+ T cell’sCD27/28 loss to be at most 12% of the population. In contrast, CD27/ 28 loss, when CD3+CD8+ T cells were incubated with tumor conditioned growth medium and TD exosomes, Immunology, Cleveland Clinic, Cleveland, OH, USA © 2013 Maybruck and Gastman; licensee BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Journal

Journal for ImmunoTherapy of Cancer – Springer Journals

Published: Nov 7, 2013

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