Metronomic cyclophosphamide eradicates large implanted GL261 gliomas by activating antitumor Cd8⁺ T-cell responses and immune memory.

ABSTRACT: Cancer chemotherapy using cytotoxic drugs can induce immunogenic tumor cell death; however, dosing regimens and schedules that enable single-agent chemotherapy to induce adaptive immune-dependent ablation of large, established tumors with activation of long-term immune memory have not been identified. Here, we investigate this issue in a syngeneic, implanted GL261 glioma model in immune-competent mice given cyclophosphamide on a 6-day repeating metronomic schedule. Two cycles of metronomic cyclophosphamide treatment induced sustained upregulation of tumor-associated CD8⁺ cytotoxic T lymphocyte (CTL) cells, natural killer (NK) cells, macrophages, and other immune cells. Expression of CTL- and NK-cell-shared effectors peaked on Day 6, and then declined by Day 9 after the second cy

SUBMITTER: Wu J 

PROVIDER: S-EPMC4485826 | biostudies-literature | 2015 Apr

REPOSITORIES: biostudies-literature