2.50
Hdl Handle:
http://hdl.handle.net/10547/578742
Title:
Oral tolerance to cancer can be abrogated by T regulatory cell inhibition
Authors:
Whelan, Maria C.; Casey, Garrett; Larkin, John O.; Guinn, Barbara-Ann; O'Sullivan, Gerald C.; Tangney, Mark
Abstract:
Oral administration of tumour cells induces an immune hypo-responsiveness known as oral tolerance. We have previously shown that oral tolerance to a cancer is tumour antigen specific, non-cross-reactive and confers a tumour growth advantage. We investigated the utilisation of regulatory T cell (Treg) depletion on oral tolerance to a cancer and its ability to control tumour growth. Balb/C mice were gavage fed homogenised tumour tissue – JBS fibrosarcoma (to induce oral tolerance to a cancer), or PBS as control. Growth of subcutaneous JBS tumours were measured; splenic tissue excised and flow cytometry used to quantify and compare systemic Tregs and T effector (Teff) cell populations. Prior to and/or following tumour feeding, mice were intraperitoneally administered anti-CD25, to inactivate systemic Tregs, or given isotype antibody as a control. Mice which were orally tolerised prior to subcutaneous tumour induction, displayed significantly higher systemic Treg levels (14% vs 6%) and faster tumour growth rates than controls (p<0.05). Complete regression of tumours were only seen after Treg inactivation and occurred in all groups - this was not inhibited by tumour feeding. The cure rates for Treg inactivation were 60% during tolerisation, 75% during tumour growth and 100% during inactivation for both tolerisation and tumour growth. Depletion of Tregs gave rise to an increased number of Teff cells. Treg depletion post-tolerisation and post-tumour induction led to the complete regression of all tumours on tumour bearing mice. Oral administration of tumour tissue, confers a tumour growth advantage and is accompanied by an increase in systemic Treg levels. The administration of anti-CD25 Ab decreased Treg numbers and caused an increase in Teffs. Most notably Treg cell inhibition overcame established oral tolerance with consequent tumor regression, especially relevant to foregut cancers where oral tolerance is likely to be induced by the shedding of tumour tissue into the gut.
Affiliation:
University College Cork; University of Bedfordshire
Citation:
Whelan, M.C., Casey, G., O. Larkin, J., Guinn, B.A., O’Sullivan, G.C., & Tangney, M. (2014) 'Oral tolerance to cancer can be abrogated by T regulatory cell inhibition.' PLoS ONE 9(5): e97602
Journal:
PLoS ONE
Issue Date:
15-May-2014
URI:
http://hdl.handle.net/10547/578742
DOI:
10.1371/journal.pone.0097602
Additional Links:
http://dx.plos.org/10.1371/journal.pone.0097602
Type:
Article
Language:
en
ISSN:
1932-6203
Sponsors:
This work was funded through a research grant to GOS and MT from Cancer Research Ireland (CRI06OSUG). MW was funded by a fellowship from the Royal College of Surgeons Edinburgh and the Royal College of Surgeons Ireland. The authors also acknowledge support from the Cork Cancer Research Centre.
Appears in Collections:
Biomedicine and Nutrition Research Group

Full metadata record

DC FieldValue Language
dc.contributor.authorWhelan, Maria C.en
dc.contributor.authorCasey, Garretten
dc.contributor.authorLarkin, John O.en
dc.contributor.authorGuinn, Barbara-Annen
dc.contributor.authorO'Sullivan, Gerald C.en
dc.contributor.authorTangney, Marken
dc.date.accessioned2015-09-25T09:30:54Zen
dc.date.available2015-09-25T09:30:54Zen
dc.date.issued2014-05-15en
dc.identifier.citationWhelan, M.C., Casey, G., O. Larkin, J., Guinn, B.A., O’Sullivan, G.C., & Tangney, M. (2014) 'Oral tolerance to cancer can be abrogated by T regulatory cell inhibition.' PLoS ONE 9(5): e97602en
dc.identifier.issn1932-6203en
dc.identifier.doi10.1371/journal.pone.0097602en
dc.identifier.urihttp://hdl.handle.net/10547/578742en
dc.description.abstractOral administration of tumour cells induces an immune hypo-responsiveness known as oral tolerance. We have previously shown that oral tolerance to a cancer is tumour antigen specific, non-cross-reactive and confers a tumour growth advantage. We investigated the utilisation of regulatory T cell (Treg) depletion on oral tolerance to a cancer and its ability to control tumour growth. Balb/C mice were gavage fed homogenised tumour tissue – JBS fibrosarcoma (to induce oral tolerance to a cancer), or PBS as control. Growth of subcutaneous JBS tumours were measured; splenic tissue excised and flow cytometry used to quantify and compare systemic Tregs and T effector (Teff) cell populations. Prior to and/or following tumour feeding, mice were intraperitoneally administered anti-CD25, to inactivate systemic Tregs, or given isotype antibody as a control. Mice which were orally tolerised prior to subcutaneous tumour induction, displayed significantly higher systemic Treg levels (14% vs 6%) and faster tumour growth rates than controls (p<0.05). Complete regression of tumours were only seen after Treg inactivation and occurred in all groups - this was not inhibited by tumour feeding. The cure rates for Treg inactivation were 60% during tolerisation, 75% during tumour growth and 100% during inactivation for both tolerisation and tumour growth. Depletion of Tregs gave rise to an increased number of Teff cells. Treg depletion post-tolerisation and post-tumour induction led to the complete regression of all tumours on tumour bearing mice. Oral administration of tumour tissue, confers a tumour growth advantage and is accompanied by an increase in systemic Treg levels. The administration of anti-CD25 Ab decreased Treg numbers and caused an increase in Teffs. Most notably Treg cell inhibition overcame established oral tolerance with consequent tumor regression, especially relevant to foregut cancers where oral tolerance is likely to be induced by the shedding of tumour tissue into the gut.en
dc.description.sponsorshipThis work was funded through a research grant to GOS and MT from Cancer Research Ireland (CRI06OSUG). MW was funded by a fellowship from the Royal College of Surgeons Edinburgh and the Royal College of Surgeons Ireland. The authors also acknowledge support from the Cork Cancer Research Centre.en
dc.language.isoenen
dc.relation.urlhttp://dx.plos.org/10.1371/journal.pone.0097602en
dc.rightsArchived with thanks to PLoS ONEen
dc.subjectcanceren
dc.subjecttumoursen
dc.subjectT-cellen
dc.subjectoral toleranceen
dc.subjectregulatory T-cellsen
dc.titleOral tolerance to cancer can be abrogated by T regulatory cell inhibitionen
dc.typeArticleen
dc.contributor.departmentUniversity College Corken
dc.contributor.departmentUniversity of Bedfordshireen
dc.identifier.journalPLoS ONEen
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