Metronomic cyclophosphamide activation of anti-tumor immunity: tumor model, mouse host, and drug schedule dependence of gene responses and their upstream regulators.

ABSTRACT:

Background

Cyclophosphamide (CPA) can activate immunogenic tumor cell death, which induces immune-based tumor ablation and long-term anti-tumor immunity in a syngeneic C57BL/6 (B6) mouse GL261 glioma model when CPA is given on a 6-day repeating metronomic schedule (CPA/6d). In contrast, we find that two other syngeneic B6 mouse tumors, LLC lung carcinoma and B16F10 melanoma, do not exhibit these drug-induced immune responses despite their intrinsic sensitivity to CPA cytotoxicity.

Methods

To elucidate underlying mechanisms, we investigated gene expression and molecular pathway changes associated with the disparate immune responsiveness of these tumors to CPA/6d treatment.

Results

Global transcriptome analysis indicated substantial elevation of basal GL261 immune infil

SUBMITTER: Wu J 

PROVIDER: S-EPMC4982114 | biostudies-literature | 2016 Aug

REPOSITORIES: biostudies-literature