Background 

Our bodies have special immune cells called macrophages. Their job is to find and eat cells that are old, damaged, or sick. To do this, the immune system looks for signals on cells. Some signals say “eat me,” and others say “don’t eat me.” One of the strongest “don’t eat me” signals is made by a protein called CD47. 

Cancer cells use this to their advantage. Even though they often give off “eat me” signals, they turn on the CD47 “don’t eat me” signal so the macrophages won’t destroy them. Because of this, cancer cells can survive and grow. Scientists have learned that blocking CD47 with special drugs called antibodies can remove the “don’t eat me” signal. This allows macrophages to attack the cancer cells. 

What This Research Proposes to Address 

The CD47 protein isn’t simple—it can exist in five slightly different forms, called isoforms. These isoforms come from a natural process called alternative splicing, where one gene can make several versions of a protein. Scientists think that not all isoforms of CD47 act as the “don’t eat me” signal. Some of them may have other important jobs in keeping healthy cells working the way they should. 

This study tested which CD47 isoform is truly responsible for the “don’t eat me” signal. The researchers used bladder cancer cells grown in the lab and mouse models that have been designed to help study bladder cancer.  

Why This Research Is Important 

It is very important to figure out which isoform of CD47 to target. If doctors use a treatment that blocks all the isoforms, it could also harm healthy cell functions that are necessary for patients’ health. By finding the exact isoform that acts as the “don’t eat me” signal, doctors can develop safer, more effective therapies. This study could also help identify which patients are most likely to benefit from CD47-based treatments. If doctors can test whether a patient has the harmful CD47 isoform, they can better predict who will respond to this type of immunotherapy. This would greatly improve the chances of success for future clinical trials using CD47-blocking drugs in bladder cancer. 

Final Report Summary

CD47 is a protein that normally protects healthy cells by sending a “don’t eat me” signal to the immune system. This signal tells the body’s defense cells not to attack. In cancer, though, tumor cells can use this same signal to hide from the immune system and avoid being destroyed. 

The CD47 protein can take on different forms, called isoforms, through a process known as alternative splicing. While many of these isoforms act as the “don’t eat me” signal, researchers believe that some may serve other important roles in how cells function. 

In this project, researchers discovered that certain isoforms of CD47 appear only in cancer cells and can even help predict how the disease might behave. They also found that looking at which isoforms are present in a patient’s tumor may help doctors know who is most likely to respond to a new treatment that blocks the CD47 “don’t eat me” signal. 

By identifying the right patients for this therapy, researchers can make clinical trials more successful and bring better, more targeted treatments to people with bladder cancer. This work brings us closer to using the body’s own defenses to fight cancer more effectively. 

Cheah, M. T., Chen, J. Y., Sahoo, D., Contreras-Trujillo, H., Volkmer, A. K., Scheeren, F. A., Volkmer, J.-P., & Weissman, I. L. (2015). CD14-expressing cancer cells establish the inflammatory and proliferative tumor microenvironment in bladder cancer. Proceedings of the National Academy of Sciences, 112(15), 4725–4730. https://doi.org/10.1073/pnas.1424795112

Pan, Y., Volkmer, J.-P., Mach, K. E., Rouse, R. V., Liu, J.-J., Sahoo, D., Chang, T. C., Metzner, T. J., Kang, L., Van De Rijn, M., Skinner, E. C., Gambhir, S. S., Weissman, I. L., & Liao, J. C. (2014). Endoscopic molecular imaging of human bladder cancer using a CD47 antibody. Science Translational Medicine, 6(260). https://doi.org/10.1126/scitranslmed.3009457

Shin, K., Lim, A., Zhao, C., Sahoo, D., Pan, Y., Spiekerkoetter, E., Liao, J. C., & Beachy, P. A. (2014). Hedgehog Signaling Restrains Bladder Cancer Progression by Eliciting Stromal Production of Urothelial Differentiation Factors. Cancer Cell, 26(4), 521–533. https://doi.org/10.1016/j.ccell.2014.09.001

None Reported as of August 2025

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