Article: B7-H3 and 4-1BBL cooperatively enhance the antitumor response of CD8 T cells in oral cancer
| Title | B7-H3 and 4-1BBL cooperatively enhance the antitumor response of CD8 T cells in oral cancer | ||||||||||
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| Authors | Yu, S2 4 Tang, J4 Wang, F4 Huang, H3 Wang, H4 Ma, P4 Zheng, L1 Zwahlen, RA1 Yang, H4 | ||||||||||
| Keywords | 4-1BBL B7-H3 CD8T cell Primary oral cancer cell | ||||||||||
| Issue Date | 2011 | ||||||||||
| Publisher | American Scientific Publishers. The Journal's web site is located at http://www.aspbs.com/science/ | ||||||||||
| Citation | Advanced Science Letters, 2011, v. 4 n. 2, p. 357-362 [How to Cite?] DOI: http://dx.doi.org/10.1166/asl.2011.1234 | ||||||||||
| Abstract | The aim of this study was to enhance the antitumor immunity of CD8 T cells directed against human oral cancer using B7-H3 and 4-1BBL gene transfer. Recombinant replication-defective adenovirus 5 (Adv) expressing human 4-1BBL, B7-H3 or 4-1BBL/B7-H3 was constructed using the two-plasmid rescue method. Primary human oral cancer cell vaccines (OCV) were prepared by treating cells with 20 μg/ml mitomycin-C after primary human oral cancer cells were infected with Adv transduced with 4-1BBL, B7-H3, 4-1BBL/B7-H3 or control Adv. Then, autologous, purified CD8 T cells were stimulated by coculture with OCV for 4 days. At the end of the culture, CD8 T cell activation was evaluated by ELISA to assay the production of IFNγ and IL-2 in the culture supernatants. Cytotoxic CD8 T cell effector function was analyzed by a 51Chromium (Cr)-release assay, and CD8 T cell proliferation was evaluated by flow cytometry and Cell Counting Kit-8 (CCK-8) assays. Primary human oral cancer cells expressed low levels of B7-H3 and 4-1BBL and weakly stimulated autologous T cells. The primary human oral cancer cell vaccine transduced with the combination of 4-1BBL with B7-H3 retroviruses resulted in significantly enhanced CD8 T cell activation and proliferation. This was associated with increased IFNγ and IL-2 production by CD8 T cells and improved CD8 T cell proliferation. CD8 T cells stimulated with the autologous B7-3/4-1BBL primary human oral cancer cell vaccine efficiently killed the autologous parental B7-H3/4-1BBL primary human oral cancer cells. Strong CD8 T cell activation, proliferation and longer survival time could be obtained by this vaccine. These data provide a mechanism for developing tumor vaccines using modified tumor cells in patients with oral cancer. © 2011 American Scientific Publishers. | ||||||||||
| ISSN | 1936-6612 | ||||||||||
| DOI | http://dx.doi.org/10.1166/asl.2011.1234 | ||||||||||
| ISI Accession Number ID | WOS:000291410900013
Funding Information: This work was supported by the National Natural Science Foundation of China (grant no. 30973339), the Guangdong Province Natural Science Foundation (grant no. 104518036002006303), the Guangdong Province Science and Technology Agency (grant no. 2010B050100007) and the foundation of Shenzhen Bureau of Science Technology and Information (grant no. JC200903180665A). | ||||||||||
| References | References in Scopus |
| dc.contributor.author | Yu, S | ||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|
| dc.contributor.author | Tang, J | ||||||||||
| dc.contributor.author | Wang, F | ||||||||||
| dc.contributor.author | Huang, H | ||||||||||
| dc.contributor.author | Wang, H | ||||||||||
| dc.contributor.author | Ma, P | ||||||||||
| dc.contributor.author | Zheng, L | ||||||||||
| dc.contributor.author | Zwahlen, RA | ||||||||||
| dc.contributor.author | Yang, H | ||||||||||
| dc.date.accessioned | 2011-07-27T01:25:25Z | ||||||||||
| dc.date.available | 2011-07-27T01:25:25Z | ||||||||||
| dc.date.issued | 2011 | ||||||||||
| dc.description.abstract | The aim of this study was to enhance the antitumor immunity of CD8 T cells directed against human oral cancer using B7-H3 and 4-1BBL gene transfer. Recombinant replication-defective adenovirus 5 (Adv) expressing human 4-1BBL, B7-H3 or 4-1BBL/B7-H3 was constructed using the two-plasmid rescue method. Primary human oral cancer cell vaccines (OCV) were prepared by treating cells with 20 μg/ml mitomycin-C after primary human oral cancer cells were infected with Adv transduced with 4-1BBL, B7-H3, 4-1BBL/B7-H3 or control Adv. Then, autologous, purified CD8 T cells were stimulated by coculture with OCV for 4 days. At the end of the culture, CD8 T cell activation was evaluated by ELISA to assay the production of IFNγ and IL-2 in the culture supernatants. Cytotoxic CD8 T cell effector function was analyzed by a 51Chromium (Cr)-release assay, and CD8 T cell proliferation was evaluated by flow cytometry and Cell Counting Kit-8 (CCK-8) assays. Primary human oral cancer cells expressed low levels of B7-H3 and 4-1BBL and weakly stimulated autologous T cells. The primary human oral cancer cell vaccine transduced with the combination of 4-1BBL with B7-H3 retroviruses resulted in significantly enhanced CD8 T cell activation and proliferation. This was associated with increased IFNγ and IL-2 production by CD8 T cells and improved CD8 T cell proliferation. CD8 T cells stimulated with the autologous B7-3/4-1BBL primary human oral cancer cell vaccine efficiently killed the autologous parental B7-H3/4-1BBL primary human oral cancer cells. Strong CD8 T cell activation, proliferation and longer survival time could be obtained by this vaccine. These data provide a mechanism for developing tumor vaccines using modified tumor cells in patients with oral cancer. © 2011 American Scientific Publishers. | ||||||||||
| dc.description.nature | Link_to_subscribed_fulltext | ||||||||||
| dc.identifier.citation | Advanced Science Letters, 2011, v. 4 n. 2, p. 357-362 [How to Cite?] DOI: http://dx.doi.org/10.1166/asl.2011.1234 | ||||||||||
| dc.identifier.doi | http://dx.doi.org/10.1166/asl.2011.1234 | ||||||||||
| dc.identifier.epage | 362 | ||||||||||
| dc.identifier.hkuros | 188024 | ||||||||||
| dc.identifier.isi | WOS:000291410900013
Funding Information: This work was supported by the National Natural Science Foundation of China (grant no. 30973339), the Guangdong Province Natural Science Foundation (grant no. 104518036002006303), the Guangdong Province Science and Technology Agency (grant no. 2010B050100007) and the foundation of Shenzhen Bureau of Science Technology and Information (grant no. JC200903180665A). | ||||||||||
| dc.identifier.issn | 1936-6612 | ||||||||||
| dc.identifier.issue | 2 | ||||||||||
| dc.identifier.scopus | eid_2-s2.0-79953109589 | ||||||||||
| dc.identifier.spage | 357 | ||||||||||
| dc.identifier.uri | http://hdl.handle.net/10722/134987 | ||||||||||
| dc.identifier.volume | 4 | ||||||||||
| dc.language | eng | ||||||||||
| dc.publisher | American Scientific Publishers. The Journal's web site is located at http://www.aspbs.com/science/ | ||||||||||
| dc.publisher.place | United States | ||||||||||
| dc.relation.ispartof | Advanced Science Letters | ||||||||||
| dc.relation.references | References in Scopus | ||||||||||
| dc.subject | 4-1BBL | ||||||||||
| dc.subject | B7-H3 | ||||||||||
| dc.subject | CD8T cell | ||||||||||
| dc.subject | Primary oral cancer cell | ||||||||||
| dc.title | B7-H3 and 4-1BBL cooperatively enhance the antitumor response of CD8 T cells in oral cancer | ||||||||||
| dc.type | Article |
Author Affiliations
- The University of Hong Kong
- Shenzhen-PKU-HKUST Medical Center
- Sun Yat-Sen University
- Peking University