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File
language
eng
Author
Tongu, Miki Center for Integrated Research in Science, Shimane University
Harashima, Nanae
Monma, Hiroyuki
Inao, Touko
Description
Several chemotherapeutic drugs have immune-modulating effects. For example, cyclophosphamide (CP) and gemcitabine (GEM) diminish immunosuppression by regulatory T cells (Tregs) and myeloid-derived suppressor cells (MDSCs), respectively. Here, we show that intermittent (metronomic) chemotherapy with low-dose CP plus GEM can induce anti-tumor T cell immunity in CT26 colon carcinoma-bearing mice. Although no significant growth suppression was observed by injections of CP (100 mg/kg) at 8-day intervals or those of CP (50 mg/kg) at 4-day intervals, CP injection (100 mg/kg) increased the frequency of tumor peptide-specific T lymphocytes in draining lymph nodes, which was abolished by two injections of CP (50 mg/kg) at a 4-day interval. Alternatively, injection of GEM (50 mg/kg) was superior to that of GEM (100 mg/kg) in suppressing tumor growth in vivo, despite the smaller dose. When CT26-bearing mice were treated with low-dose (50 mg/kg) CP plus (50 mg/kg) GEM at 8-day intervals, tumor growth was suppressed without impairing T cell function; the effect was mainly T cell dependent. The metronomic combination chemotherapy cured one-third of CT26-bearing mice that acquired tumor-specific T cell immunity. The combination therapy decreased Foxp3 and arginase-1 mRNA levels but increased IFN-γ mRNA expression in tumor tissues. The percentages of tumor-infiltrating CD45^+ cells, especially Gr-1^<high> CD11b^+ MDSCs, were decreased. These results indicate that metronomic chemotherapy with low-dose CP plus GEM is a promising protocol to mitigate totally Treg- and MDSC-mediated immunosuppression and elicit anti-tumor T cell immunity in vivo.
Subject
Cyclophosphamide
Gemcitabine
T cell immunity
MDSC
Treg
Journal Title
Cancer Immunology and Immunotherapy
Volume
62
Issue
2
Start Page
383
End Page
391
ISSN
03407004
Published Date
2013-02
DOI
DOI Date
2017-03-15
PubMed ID
NCID
AA00598499
Publisher
Springer
NII Type
Journal Article
Format
PDF
Rights
© Springer-Verlag 2012
Text Version
著者版
Gyoseki ID
e22203
e20190
OAI-PMH Set
Interdisciplinary Center for Science Research
School of Medicine, Faculty of Medicine
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