Defects in the acquisition of tumor-killing capability of CD8+ cytotoxic T cells in streptozotocin-induced diabetic mice.
Emerging evidences have shown that diabetes mellitus not only raises risk but also heightens mortality rate of cancer. It is not clear, however, whether antitumor CD8+ cytotoxic T lymphocyte (CTL) response is down-modulated in diabetic hosts. We investigated the impact of hyperglycemia on CTLs'...
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| Format: | Article |
| Language: | English |
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Public Library of Science (PLoS)
2014-01-01
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| Series: | PLoS ONE |
| Online Access: | http://europepmc.org/articles/PMC4229103?pdf=render |
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| author | Shu-Ching Chen Yu-Chia Su Ya-Ting Lu Patrick Chow-In Ko Pei-Yu Chang Hung-Ju Lin Hong-Nerng Ho Yo-Ping Lai |
| author_facet | Shu-Ching Chen Yu-Chia Su Ya-Ting Lu Patrick Chow-In Ko Pei-Yu Chang Hung-Ju Lin Hong-Nerng Ho Yo-Ping Lai |
| author_sort | Shu-Ching Chen |
| collection | DOAJ |
| description | Emerging evidences have shown that diabetes mellitus not only raises risk but also heightens mortality rate of cancer. It is not clear, however, whether antitumor CD8+ cytotoxic T lymphocyte (CTL) response is down-modulated in diabetic hosts. We investigated the impact of hyperglycemia on CTLs' acquisition of tumor-killing capability by utilizing streptozotocin-induced diabetic (STZ-diabetic) mice. Murine diabetes was induced by intraperitoneal injection of STZ (200 mg/kg) in C57BL/6 mice, 2C-T cell receptor (TCR) transgenic and P14-TCR transgenic mice. The study found that, despite harboring intact proliferative capacity measured with CFSE labeling and MTT assay, STZ-diabetic CD8+ CTLs displayed impaired effector functions. After stimulation, STZ-diabetic CD8+ CTLs produced less perforin and TNFα assessed by intracellular staining, as well as expressed less CD103 protein. Furthermore, adoptive transfer of STZ-diabetic P14 CD8+ effector cells showed an insufficient recruitment to the B16.gp33 melanoma and inadequate production of perforin, granzyme B and TNFα determined by immunohistochemistry in the tumor milieu. As a result, STZ-diabetic CD8+ effector cells were neither able to eliminate tumor nor to improve survival of tumor-bearing mice. Taken together, our data suggest that CD8+ CTLs are crippled to infiltrate into tumors and thus fail to acquire tumor-killing capability in STZ-diabetic hosts. |
| first_indexed | 2024-12-22T14:11:59Z |
| format | Article |
| id | doaj.art-0b55c2794caf4f56a7ff2e1349b07306 |
| institution | Directory Open Access Journal |
| issn | 1932-6203 |
| language | English |
| last_indexed | 2024-12-22T14:11:59Z |
| publishDate | 2014-01-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS ONE |
| spelling | doaj.art-0b55c2794caf4f56a7ff2e1349b073062022-12-21T18:23:11ZengPublic Library of Science (PLoS)PLoS ONE1932-62032014-01-01911e10996110.1371/journal.pone.0109961Defects in the acquisition of tumor-killing capability of CD8+ cytotoxic T cells in streptozotocin-induced diabetic mice.Shu-Ching ChenYu-Chia SuYa-Ting LuPatrick Chow-In KoPei-Yu ChangHung-Ju LinHong-Nerng HoYo-Ping LaiEmerging evidences have shown that diabetes mellitus not only raises risk but also heightens mortality rate of cancer. It is not clear, however, whether antitumor CD8+ cytotoxic T lymphocyte (CTL) response is down-modulated in diabetic hosts. We investigated the impact of hyperglycemia on CTLs' acquisition of tumor-killing capability by utilizing streptozotocin-induced diabetic (STZ-diabetic) mice. Murine diabetes was induced by intraperitoneal injection of STZ (200 mg/kg) in C57BL/6 mice, 2C-T cell receptor (TCR) transgenic and P14-TCR transgenic mice. The study found that, despite harboring intact proliferative capacity measured with CFSE labeling and MTT assay, STZ-diabetic CD8+ CTLs displayed impaired effector functions. After stimulation, STZ-diabetic CD8+ CTLs produced less perforin and TNFα assessed by intracellular staining, as well as expressed less CD103 protein. Furthermore, adoptive transfer of STZ-diabetic P14 CD8+ effector cells showed an insufficient recruitment to the B16.gp33 melanoma and inadequate production of perforin, granzyme B and TNFα determined by immunohistochemistry in the tumor milieu. As a result, STZ-diabetic CD8+ effector cells were neither able to eliminate tumor nor to improve survival of tumor-bearing mice. Taken together, our data suggest that CD8+ CTLs are crippled to infiltrate into tumors and thus fail to acquire tumor-killing capability in STZ-diabetic hosts.http://europepmc.org/articles/PMC4229103?pdf=render |
| spellingShingle | Shu-Ching Chen Yu-Chia Su Ya-Ting Lu Patrick Chow-In Ko Pei-Yu Chang Hung-Ju Lin Hong-Nerng Ho Yo-Ping Lai Defects in the acquisition of tumor-killing capability of CD8+ cytotoxic T cells in streptozotocin-induced diabetic mice. PLoS ONE |
| title | Defects in the acquisition of tumor-killing capability of CD8+ cytotoxic T cells in streptozotocin-induced diabetic mice. |
| title_full | Defects in the acquisition of tumor-killing capability of CD8+ cytotoxic T cells in streptozotocin-induced diabetic mice. |
| title_fullStr | Defects in the acquisition of tumor-killing capability of CD8+ cytotoxic T cells in streptozotocin-induced diabetic mice. |
| title_full_unstemmed | Defects in the acquisition of tumor-killing capability of CD8+ cytotoxic T cells in streptozotocin-induced diabetic mice. |
| title_short | Defects in the acquisition of tumor-killing capability of CD8+ cytotoxic T cells in streptozotocin-induced diabetic mice. |
| title_sort | defects in the acquisition of tumor killing capability of cd8 cytotoxic t cells in streptozotocin induced diabetic mice |
| url | http://europepmc.org/articles/PMC4229103?pdf=render |
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