Defects in the acquisition of tumor-killing capability of CD8+ cytotoxic T cells in streptozotocin-induced diabetic mice

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

Research output: Contribution to journalArticle

3 Citations (Scopus)

Abstract

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 streptozotocininduced 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 TNFa 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.

Original languageEnglish
Article numbere109961
JournalPLoS ONE
Volume9
Issue number11
DOIs
Publication statusPublished - Nov 12 2014

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CD Antigens
Integrin alpha Chains
T-cells
Cell proliferation
Streptozocin
T-Cell Antigen Receptor
Tumors
Animals
Cytokines
Defects
Medical problems
Bearings (structural)
Perforin
Labeling
Assays

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)
  • Agricultural and Biological Sciences(all)

Cite this

Chen, S. C., Su, Y. C., Lu, Y. T., Ko, P. C. I., Chang, P. Y., Lin, H. J., ... Lai, Y. P. (2014). Defects in the acquisition of tumor-killing capability of CD8+ cytotoxic T cells in streptozotocin-induced diabetic mice. PLoS ONE, 9(11), [e109961]. https://doi.org/10.1371/journal.pone.0109961

Defects in the acquisition of tumor-killing capability of CD8+ cytotoxic T cells in streptozotocin-induced diabetic mice. / Chen, Shu Ching; Su, Yu Chia; Lu, Ya Ting; Ko, Patrick Chow In; Chang, Pei Yu; Lin, Hung Ju; Ho, Hong Nerng; Lai, Yo Ping.

In: PLoS ONE, Vol. 9, No. 11, e109961, 12.11.2014.

Research output: Contribution to journalArticle

Chen, Shu Ching ; Su, Yu Chia ; Lu, Ya Ting ; Ko, Patrick Chow In ; Chang, Pei Yu ; Lin, Hung Ju ; Ho, Hong Nerng ; Lai, Yo Ping. / Defects in the acquisition of tumor-killing capability of CD8+ cytotoxic T cells in streptozotocin-induced diabetic mice. In: PLoS ONE. 2014 ; Vol. 9, No. 11.
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