File Download
  Links for fulltext
     (May Require Subscription)
Supplementary

Article: Antigen spreading-induced CD8+T cells confer protection against the lethal challenge of wild-type malignant mesothelioma by eliminating myeloid-derived suppressor cells

TitleAntigen spreading-induced CD8+T cells confer protection against the lethal challenge of wild-type malignant mesothelioma by eliminating myeloid-derived suppressor cells
Authors
KeywordsAntigen spreading
CD8+T cells
Immune response
Immunity
Immunology and Microbiology Section
MDSCs
Mesothelioma
Vaccination
Issue Date2015
PublisherImpact Journals LLC. The Journal's web site is located at http://www.impactjournals.com/oncotarget/index.html
Citation
Oncotarget, 2015, v. 6 n. 32, p. 32426-32438 How to Cite?
AbstractA key focus in cancer immunotherapy is to investigate the mechanism of efficacious vaccine responses. Using HIV-1 GAG-p24 in a model PD1-based DNA vaccine, we recently reported that vaccine-elicited CD8+ T cells conferred complete prevention and therapeutic cure of AB1-GAG malignant mesothelioma in immunocompetent BALB/c mice. Here, we further investigated the efficacy and correlation of protection on the model vaccine-mediated antigen spreading against wild-type AB1 (WT-AB1) mesothelioma. We found that this vaccine was able to protect mice completely from three consecutive lethal challenges of AB1-GAG mesothelioma. Through antigen spreading these animals also developed tumor-specific cytotoxic CD8+ T cells, but neither CD4+ T cells nor antibodies, rejecting WT-AB1 mesothelioma. A majority of these protected mice (90%) were also completely protected against the lethal WT-AB1 challenge. Adoptive cell transfer experiments further demonstrated that antigen spreading-induced CD8+ T cells conferred efficacious therapeutic effects against established WT-AB1 mesothelioma and prevented the increase of exhausted PD-1+ and Tim-3+ CD8+ T cells. A significant inverse correlation was found between the frequency of functional PD1-Tim3- CD8+ T cells and that of MDSCs or tumor mass in vivo. Mechanistically, we found that WT-AB1 mesothelioma induced predominantly polymorphonuclear (PMN) MDSCs in vivo. In co-cultures with efficacious CD8+ T cells, a significant number of PMN-MDSCs underwent apoptosis in a dose-dependent way. Our findings indicate that efficacious CD8+ T cells capable of eliminating both tumor cells and MDSCs are likely necessary for fighting wild-type malignant mesothelioma.
Persistent Identifierhttp://hdl.handle.net/10722/223861
ISSN
2015 Impact Factor: 5.008
2015 SCImago Journal Rankings: 2.294
PubMed Central ID
ISI Accession Number ID

 

DC FieldValueLanguage
dc.contributor.authorYu, Z-
dc.contributor.authorTan, Z-
dc.contributor.authorLee, BK-
dc.contributor.authorTang, J-
dc.contributor.authorWu, X-
dc.contributor.authorCheung, KW-
dc.contributor.authorLo, NTL-
dc.contributor.authorMan, K-
dc.contributor.authorLiu, L-
dc.contributor.authorChen, Z-
dc.date.accessioned2016-03-18T02:30:05Z-
dc.date.available2016-03-18T02:30:05Z-
dc.date.issued2015-
dc.identifier.citationOncotarget, 2015, v. 6 n. 32, p. 32426-32438-
dc.identifier.issn1949-2553-
dc.identifier.urihttp://hdl.handle.net/10722/223861-
dc.description.abstractA key focus in cancer immunotherapy is to investigate the mechanism of efficacious vaccine responses. Using HIV-1 GAG-p24 in a model PD1-based DNA vaccine, we recently reported that vaccine-elicited CD8+ T cells conferred complete prevention and therapeutic cure of AB1-GAG malignant mesothelioma in immunocompetent BALB/c mice. Here, we further investigated the efficacy and correlation of protection on the model vaccine-mediated antigen spreading against wild-type AB1 (WT-AB1) mesothelioma. We found that this vaccine was able to protect mice completely from three consecutive lethal challenges of AB1-GAG mesothelioma. Through antigen spreading these animals also developed tumor-specific cytotoxic CD8+ T cells, but neither CD4+ T cells nor antibodies, rejecting WT-AB1 mesothelioma. A majority of these protected mice (90%) were also completely protected against the lethal WT-AB1 challenge. Adoptive cell transfer experiments further demonstrated that antigen spreading-induced CD8+ T cells conferred efficacious therapeutic effects against established WT-AB1 mesothelioma and prevented the increase of exhausted PD-1+ and Tim-3+ CD8+ T cells. A significant inverse correlation was found between the frequency of functional PD1-Tim3- CD8+ T cells and that of MDSCs or tumor mass in vivo. Mechanistically, we found that WT-AB1 mesothelioma induced predominantly polymorphonuclear (PMN) MDSCs in vivo. In co-cultures with efficacious CD8+ T cells, a significant number of PMN-MDSCs underwent apoptosis in a dose-dependent way. Our findings indicate that efficacious CD8+ T cells capable of eliminating both tumor cells and MDSCs are likely necessary for fighting wild-type malignant mesothelioma.-
dc.languageeng-
dc.publisherImpact Journals LLC. The Journal's web site is located at http://www.impactjournals.com/oncotarget/index.html-
dc.relation.ispartofOncotarget-
dc.rightsThis work is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License.-
dc.subjectAntigen spreading-
dc.subjectCD8+T cells-
dc.subjectImmune response-
dc.subjectImmunity-
dc.subjectImmunology and Microbiology Section-
dc.subjectMDSCs-
dc.subjectMesothelioma-
dc.subjectVaccination-
dc.titleAntigen spreading-induced CD8+T cells confer protection against the lethal challenge of wild-type malignant mesothelioma by eliminating myeloid-derived suppressor cells-
dc.typeArticle-
dc.identifier.emailTan, Z: zwtan@hku.hk-
dc.identifier.emailCheung, KW: fayekw@hku.hk-
dc.identifier.emailLo, NTL: natlo92@hku.hk-
dc.identifier.emailMan, K: kwanman@hku.hk-
dc.identifier.emailLiu, L: liuli71@hkucc.hku.hk-
dc.identifier.emailChen, Z: zchenai@hku.hk-
dc.identifier.authorityMan, K=rp00417-
dc.identifier.authorityLiu, L=rp00268-
dc.identifier.authorityChen, Z=rp00243-
dc.description.naturepublished_or_final_version-
dc.identifier.doi10.18632/oncotarget.5856-
dc.identifier.pmid26431275-
dc.identifier.pmcidPMC4741703-
dc.identifier.scopuseid_2-s2.0-84946031852-
dc.identifier.hkuros257269-
dc.identifier.volume6-
dc.identifier.issue32-
dc.identifier.spage32426-
dc.identifier.epage32438-
dc.identifier.isiWOS:000363186600027-
dc.publisher.placeUnited States-
dc.identifier.issnl1949-2553-

Export via OAI-PMH Interface in XML Formats


OR


Export to Other Non-XML Formats