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Study shows cancer therapy may work in new and unexpected way

The body’s immune cells constantly work to achieve the right balance between being shoot-first, ask-questions-later enforcers that efficiently wipe out all diseased and infected cells (but risk hitting innocent, healthy cells and causing autoimmune disorders), and being easy-going, small town sheriffs that let healthy cells happily get on with their lives (but risk being over-matched by homegrown or invading pathogens). One way to achieve this balance is to introduce “immune checkpoints” -- proteins displayed on the surface of healthy cells that connect with receptors on highly active immune cells to tell them, “Settle down -- we’re the good guys.”

It seems inevitable that such a system would start being used by the bad guys. And indeed, researchers have known for about ten years that cancer cells display a protein called PD-L1 (programmed death ligand-1), which connects with a PD-1 receptor on T cells to give those immune cells the message “Nothing going on here, you can move along.” A number of successful cancer therapies have been designed to work by blocking that safe-conduct pass and unleashing T cells to attack cancer cells with gusto.

Now researchers in the laboratory of professor Irv Weissman, MD, have shown that these therapies may not work exactly as everyone thought. In addition to blocking T-cell attacks on cancer, PD-1 signaling also blocks attack by other immune cells called macrophages. They published this work today in the journal Nature.

The result could have practical implications, as I outline in our news release on this research:

…antibodies to PD-1 or PD-L1 may be more potent and broadly effective than previously thought. 'In order for T cells to attack cancer when you take the brakes off with antibodies, you need to start with a population of T cells that have learned to recognize specific cancer cells in the first place,' Weissman said. 'Macrophage cells are part of the innate immune system, which means they should be able to recognize every kind of cancer in every patient.'

Or, as Sydney Gordon, graduate student and lead author on the research, notes, new therapies could be designed to promote either the T-cell part of the attack on cancer or the macrophage part -- whichever is more effective.

Previously: Stanford's Ronald Levy offers peek at future of cancer therapy and Cancer-causing gene also helps tumors dodge immune system
Image of macrophage by Shutterstock

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