Macrophages are cells of the immune system that protect the host from invading pathogens. But in cancer, macrophages can be “hijacked” by tumors, and made to support their malignant growth and spread. This is a drawback for a major cancer treatment, immunotherapy, which turns the body’s immune system against the tumor. EPFL scientists, working with colleagues at the Roche Innovation Centers in Munich and Basel, have now identified a molecular “switch” that can convert the “hijacked” macrophages into cells that can stimulate the immune system to fight the growth and spread of cancer. The work is published in Nature Cell Biology.
Along with attacking foreign pathogens like bacteria, macrophages also help the body’s organs develop and its wounds heal. Their own behavior is fine-tuned by small molecules that they produce, called microRNAs.
When a tumor begins to develop, macrophages attempt to block its growth. But often tumors hijack them and convert them into what are known as “tumor-associated macrophages”, or TAMs for short.
Now corrupted, TAMs use their microRNAs to shield the tumor from the patient’s immune system, helping it grow and metastasize. This phenomenon is common across many tumor types. It is one of the major obstacles in treating cancer, and often leads to a poor prognosis for the patient.
Michele De Palma’s team at EPFL found how to reclaim TAMs. The researchers genetically modified TAMs to remove their ability to produce microRNAs. As a result, the TAMs were reprogrammed dramatically. Instead of protecting the tumor, the TAMs now signaled the presence of the tumor to the immune system, triggering attacks against it – and did so very efficiently.