Oral tolerance to cancer can be abrogated by T regulatory cell inhibition
dc.contributor.author | Whelan, Maria C. | |
dc.contributor.author | Casey, Garrett | |
dc.contributor.author | Larkin, John O. | |
dc.contributor.author | Guinn, Barbara-Ann | |
dc.contributor.author | O'Sullivan, Gerald C. | |
dc.contributor.author | Tangney, Mark | |
dc.contributor.funder | Cancer Research Ireland | |
dc.contributor.funder | Royal College of Surgeons of Edinburgh, United Kingdom | |
dc.contributor.funder | Royal College of Surgeons in Ireland | |
dc.contributor.funder | Cork Cancer Research Centre, College of Medicine and Health, University College Cork | |
dc.date.accessioned | 2016-02-17T11:44:40Z | |
dc.date.available | 2016-02-17T11:44:40Z | |
dc.date.issued | 2014 | |
dc.description.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. | en |
dc.description.sponsorship | Cancer Research Ireland (CRI06OSUG); Royal College of Surgeons of Edinburgh, United Kingdom (Fellowship); Royal College of Surgeons in Ireland (Fellowship) | en |
dc.description.status | Peer reviewed | en |
dc.description.version | Published Version | en |
dc.format.mimetype | application/pdf | en |
dc.identifier.articleid | e97602 | |
dc.identifier.citation | Whelan MC, Casey G, Larkin JO, Guinn B-a, O'Sullivan GC, Tangney M (2014) Oral Tolerance to Cancer Can Be Abrogated by T Regulatory Cell Inhibition. PLoS ONE 9(5): e97602. doi:10.1371/journal.pone.0097602 | |
dc.identifier.doi | 10.1371/journal.pone.0097602 | |
dc.identifier.issn | 1932-6203 | |
dc.identifier.issued | 5 | en |
dc.identifier.journaltitle | PLOS ONE | en |
dc.identifier.uri | https://hdl.handle.net/10468/2339 | |
dc.identifier.volume | 9 | en |
dc.language.iso | en | en |
dc.publisher | Public Library of Science | en |
dc.rights | © 2015 Whelan et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited | en |
dc.rights.uri | http://creativecommons.org/licenses/by/4.0/ | en |
dc.subject | Immune tolerance | en |
dc.subject | Immunotherapy | en |
dc.subject | Esophageal | en |
dc.subject | Induction | en |
dc.subject | Survival | en |
dc.title | Oral tolerance to cancer can be abrogated by T regulatory cell inhibition | en |
dc.type | Article (peer-reviewed) | en |
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