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Article: Vaccine-elicited CD8+ T cells cure mesothelioma by overcoming tumor-induced immunosuppressive environment

TitleVaccine-elicited CD8+ T cells cure mesothelioma by overcoming tumor-induced immunosuppressive environment
Authors
Issue Date2014
PublisherAmerican Association for Cancer Research. The Journal's web site is located at http://cancerres.aacrjournals.org/
Citation
Cancer Research, 2014, v. 74 n. 21, p. 6010-6021 How to Cite?
AbstractEradicating malignant tumors by vaccine-elicited host immunity remains a major medical challenge. To date, correlates of immune protection remain unknown for malignant mesothelioma. In this study, we demonstrated that antigen-specific CD8+ T-cell immune response correlates with the elimination of malignant mesothelioma by a model PD-1–based DNA vaccine. Unlike the nonprotective tumor antigen WT1-based DNA vaccines, the model vaccine showed complete and long-lasting protection against lethal mesothelioma challenge in immunocompetent BALB/c mice. Furthermore, it remained highly immunogenic in tumor-bearing animals and led to therapeutic cure of preexisting mesothelioma. T-cell depletion and adoptive transfer experiments revealed that vaccine-elicited CD8+ T cells conferred to the protective efficacy in a dose-dependent way. Also, these CD8+ T cells functioned by releasing inflammatory IFNγ and TNFα in the vicinity of target cells as well as by initiating TRAIL-directed tumor cell apoptosis. Importantly, repeated DNA vaccinations, a major advantage over live-vectored vaccines with issues of preexisting immunity, achieve an active functional state, not only preventing the rise of exhausted PD-1+ and Tim-3+ CD8+ T cells but also suppressing tumor-induced myeloid-derived suppressive cells and Treg cells, with the frequency of antigen-specific CD8+ T cells inversely correlating with tumor mass. Our results provide new insights into quantitative and qualitative requirements of vaccine-elicited functional CD8+ T cells in cancer prevention and immunotherapy. Cancer Res; 74(21); 6010–21. ©2014 AACR.
Persistent Identifierhttp://hdl.handle.net/10722/207255
ISSN
2017 Impact Factor: 9.13
2015 SCImago Journal Rankings: 5.372
ISI Accession Number ID

 

DC FieldValueLanguage
dc.contributor.authorTan, Z-
dc.contributor.authorZhou, J-
dc.contributor.authorCheung, AKL-
dc.contributor.authorYu, Z-
dc.contributor.authorCheung, KW-
dc.contributor.authorLiang, J-
dc.contributor.authorWang, H-
dc.contributor.authorLee, BK-
dc.contributor.authorMan, K-
dc.contributor.authorLiu, L-
dc.contributor.authorYuen, KY-
dc.contributor.authorChen, Z-
dc.date.accessioned2014-12-19T09:44:56Z-
dc.date.available2014-12-19T09:44:56Z-
dc.date.issued2014-
dc.identifier.citationCancer Research, 2014, v. 74 n. 21, p. 6010-6021-
dc.identifier.issn0008-5472-
dc.identifier.urihttp://hdl.handle.net/10722/207255-
dc.description.abstractEradicating malignant tumors by vaccine-elicited host immunity remains a major medical challenge. To date, correlates of immune protection remain unknown for malignant mesothelioma. In this study, we demonstrated that antigen-specific CD8+ T-cell immune response correlates with the elimination of malignant mesothelioma by a model PD-1–based DNA vaccine. Unlike the nonprotective tumor antigen WT1-based DNA vaccines, the model vaccine showed complete and long-lasting protection against lethal mesothelioma challenge in immunocompetent BALB/c mice. Furthermore, it remained highly immunogenic in tumor-bearing animals and led to therapeutic cure of preexisting mesothelioma. T-cell depletion and adoptive transfer experiments revealed that vaccine-elicited CD8+ T cells conferred to the protective efficacy in a dose-dependent way. Also, these CD8+ T cells functioned by releasing inflammatory IFNγ and TNFα in the vicinity of target cells as well as by initiating TRAIL-directed tumor cell apoptosis. Importantly, repeated DNA vaccinations, a major advantage over live-vectored vaccines with issues of preexisting immunity, achieve an active functional state, not only preventing the rise of exhausted PD-1+ and Tim-3+ CD8+ T cells but also suppressing tumor-induced myeloid-derived suppressive cells and Treg cells, with the frequency of antigen-specific CD8+ T cells inversely correlating with tumor mass. Our results provide new insights into quantitative and qualitative requirements of vaccine-elicited functional CD8+ T cells in cancer prevention and immunotherapy. Cancer Res; 74(21); 6010–21. ©2014 AACR.-
dc.languageeng-
dc.publisherAmerican Association for Cancer Research. The Journal's web site is located at http://cancerres.aacrjournals.org/-
dc.relation.ispartofCancer Research-
dc.titleVaccine-elicited CD8+ T cells cure mesothelioma by overcoming tumor-induced immunosuppressive environment-
dc.typeArticle-
dc.identifier.emailTan, Z: zwtan@hku.hk-
dc.identifier.emailCheung, AKL: allenc@hku.hk-
dc.identifier.emailYu, Z: yuzhe19@hku.hk-
dc.identifier.emailCheung, KW: fayekw@hku.hk-
dc.identifier.emailLiang, J: jayliang@hku.hk-
dc.identifier.emailWang, H: hbwang@hkucc.hku.hk-
dc.identifier.emailMan, K: kwanman@hku.hk-
dc.identifier.emailLiu, L: liuli71@hkucc.hku.hk-
dc.identifier.emailYuen, KY: kyyuen@hkucc.hku.hk-
dc.identifier.emailChen, Z: zchenai@hku.hk-
dc.identifier.authorityMan, K=rp00417-
dc.identifier.authorityLiu, L=rp00268-
dc.identifier.authorityYuen, KY=rp00366-
dc.identifier.authorityChen, Z=rp00243-
dc.description.naturelink_to_OA_fulltext-
dc.identifier.doi10.1158/0008-5472.CAN-14-0473-
dc.identifier.pmid25125656-
dc.identifier.scopuseid_2-s2.0-84909594602-
dc.identifier.hkuros241989-
dc.identifier.hkuros255217-
dc.identifier.volume74-
dc.identifier.issue21-
dc.identifier.spage6010-
dc.identifier.epage6021-
dc.identifier.isiWOS:000344756800009-
dc.publisher.placeUnited States-

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