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Combination effect of regulatory T-cell depletion and ionizing radiation in mouse models of lung and colon cancer.
- Source :
-
International journal of radiation oncology, biology, physics [Int J Radiat Oncol Biol Phys] 2015 Jun 01; Vol. 92 (2), pp. 390-8. Date of Electronic Publication: 2015 Mar 05. - Publication Year :
- 2015
-
Abstract
- Purpose: To investigate the potential of low-dose cyclophosphamide (LD-CTX) and anti-CD25 antibody to prevent activation of regulatory T cells (Tregs) during radiation therapy.<br />Methods and Materials: We used LD-CTX and anti-CD25 monoclonal antibody as a means to inhibit Tregs and improve the therapeutic effect of radiation in a mouse model of lung and colon cancer. Mice were irradiated on the tumor mass of the right leg and treated with LD-CTX and anti-CD25 antibody once per week for 3 weeks.<br />Results: Combined treatment of LD-CTX or anti-CD25 antibody with radiation significantly decreased Tregs in the spleen and tumor compared with control and irradiation only in both lung and colon cancer. Combinatorial treatments resulted in a significant increase in the effector T cells, longer survival rate, and suppressed irradiated and distal nonirradiated tumor growth. Specifically, the combinatorial treatment of LD-CTX with radiation resulted in outstanding regression of local and distant tumors in colon cancer, and almost all mice in this group survived until the end of the study.<br />Conclusions: Our results suggest that Treg depletion strategies may enhance radiation-mediated antitumor immunity and further improve outcomes after radiation therapy.<br /> (Copyright © 2015 Elsevier Inc. All rights reserved.)
- Subjects :
- Animals
Colonic Neoplasms immunology
Colonic Neoplasms mortality
Combined Modality Therapy
Lung Neoplasms immunology
Lung Neoplasms mortality
Male
Mice
Mice, Inbred BALB C
Antineoplastic Agents, Alkylating administration & dosage
Colonic Neoplasms radiotherapy
Cyclophosphamide administration & dosage
Immunosuppressive Agents administration & dosage
Interleukin-2 Receptor alpha Subunit antagonists & inhibitors
Lung Neoplasms radiotherapy
T-Lymphocytes, Regulatory drug effects
T-Lymphocytes, Regulatory radiation effects
Subjects
Details
- Language :
- English
- ISSN :
- 1879-355X
- Volume :
- 92
- Issue :
- 2
- Database :
- MEDLINE
- Journal :
- International journal of radiation oncology, biology, physics
- Publication Type :
- Academic Journal
- Accession number :
- 25754628
- Full Text :
- https://doi.org/10.1016/j.ijrobp.2015.01.011