Research ArticleRadiation Therapy

Radioprotection in Normal Tissue and Delayed Tumor Growth by Blockade of CD47 Signaling

Science Translational Medicine  21 Oct 2009:
Vol. 1, Issue 3, pp. 3ra7
DOI: 10.1126/scitranslmed.3000139

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Editor's Summary

One major caveat of radiation therapy in cancer treatment is that the effective dose delivered to the individual is oftentimes necessarily limited to avoid major side effects that arise from collateral damage inflicted on surrounding normal tissue. Efforts to devise methods to sensitize tumor tissue to radiation injury or to protect normal tissue by scavenging for reactive by-products of radiation have only been moderately successful, as their broad clinical utility is hampered by a lack of specificity or by toxicity. Now, a team of researchers describes an approach to protecting normal human cells from high-dose radiation damage while, at the same time, increasing the sensitivity of tumor cells to radiation.

We know that the pathway triggered by the secretory glycoprotein thrombospondin-1 (TSP1) and its corresponding membrane receptor CD47 in response to injury limits the survival of vascular cells and tissues. In this work, Roberts et al. have devised a strategy by which the systemic blockade of TSP1 and its receptor CD47 inhibits downstream signaling functions to protect against radiation injury the highly radiation-sensitive endothelial cells that line the lumen of the vasculature. More important, they show in mice injected with human tumors that suppression of CD47 by systemic administration of an antisense CD47 morpholino can sensitize the tumors to high-dose radiation therapy while keeping collateral damage at bay, exemplified in part by the resilience of the skin, muscle, and bone to radiation injury. Their experiments simultaneously show a significant delay in the time that these tumors take to grow back. This phenomenon remains to be explained, but there is an improvement in vascular function in irradiated, CD47-suppressed mice, and, at the cellular level, in vivo stem cells are still viable and proliferate, whereas peripheral immune cells, which infiltrate the inflammatory tumor microenvironment, are protected and recruited to the site.

Although it remains speculative how CD47 participates in antitumor immunity within this experimental context, combined treatment of high-dose radiation and CD47 suppression in these translational studies suggests that a more aggressive therapeutic irradiation strategy with concurrent protection of neighboring normal tissue is possible. Testing the effectiveness of such a treatment strategy will be required to see whether this approach is useful.


  • Citation: J. B. Maxhimer, D. R. Soto-Pantoja, L. A. Ridnour, H. B. Shih, W. G. DeGraff, M. Tsokos, D. A. Wink, J. S. Isenberg, D. D. Roberts, Radioprotection in normal tissue and delayed tumor growth by blockade of CD47 signaling. Sci. Transl. Med. 1, 3ra7 (2009).