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Chloroquine engages the immune system to eradicate irradiated breast tumors in mice. | LitMetric

Chloroquine engages the immune system to eradicate irradiated breast tumors in mice.

Int J Radiat Oncol Biol Phys

Department of Radiation Oncology, David Geffen School of Medicine at UCLA, Los Angeles, California.

Published: November 2013

AI Article Synopsis

Article Abstract

Purpose: This study used chloroquine to direct radiation-induced tumor cell death pathways to harness the antitumor activity of the immune system.

Methods And Materials: Chloroquine given immediately after tumor irradiation increased the cure rate of MCaK breast cancer in C3H mice. Chloroquine blocked radiation-induced autophagy and drove MCaK cells into a more rapid apoptotic and more immunogenic form of cell death.

Results: Chloroquine treatment made irradiated tumor vaccines superior at inducing strong interferon gamma-associated immune responses in vivo and protecting mice from further tumor challenge. In vitro, chloroquine slowed antigen uptake and degradation by dendritic cells, although T-cell stimulation was unaffected.

Conclusions: This study illustrates a novel approach to improve the efficacy of breast cancer radiation therapy by blocking endosomal pathways, which enhances radiation-induced cell death within the field and drives antitumor immunity to assist therapeutic cure. The study illuminates and merges seemingly disparate concepts regarding the importance of autophagy in cancer therapy.

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.ijrobp.2013.07.024DOI Listing

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