Defects in the Acquisition of Tumor-Killing Capability of CD8+ Cytotoxic T Cells in Streptozotocin-induced Diabetic Mice

Diabetes mellitus has been known not only to associate with an increased risk of cancers but also heighten the mortality rate. However, whether the antitumor CD8+ T cell immunity is down-modulated in diabetic hosts remains not clear. Our data depicts that, even harboring intact proliferative capacity, streptozotocin-induced diabetic (STZ-diabetic) CD8+ T cells produce less perforin and TNFa and express less CD103 protein after stimulation. In advance, adoptive transfer of STZ-diabetic P14 CD8+ T effector cells show insufficient infiltration to B16.gp33 melanoma in vivo and inadequate production of perforin, granzyme B and TNFa in the tumor. STZ-diabetic CD8+ CTLs are neither able to eliminate tumor nor improve survival of tumor-bearing mice. In conclusion, diabetic CD8+ CTLs are crippled to infiltrate into tumors and fail to acquire tumor-killing capability. These new findings will have major impact on elucidating how diabetic CD8+ T cells are dysregulated and impeded by the acquisition of full effector functions and tumor-killing capability. With such exciting findings, we believe that our study will advance strategies of inducing protective antitumor immunity in diabetic hosts.