Radiation therapy not only kills cancer cells, but also helps to activate the immune system against their future proliferation. However, this immune response is often not strong enough to be able to cure tumours, and even when it is, its effect is limited to the area that has been irradiated. Now, however, research to be presented to the ESTRO 35 conference has shown that the addition of an immune system-strengthening compound can extend the radiation therapy-induced immune response against the tumour sites and that this response even has an effect on tumours outside the radiation field.
Ms Nicolle Rekers, MSc, from the Department of Radiation Oncology, Maastricht University Medical Centre, Maastricht, The Netherlands, will describe to the conference how a combination of radiation therapy and L19-IL2, an immunotherapy agent, can increase significantly the immune response when given to mice with primary colorectal tumours. L19-IL2 is a combination of an antibody that targets the tumour blood vessels and a cytokine, a small protein important in cell signalling in the immune system.
The researchers found not only that the mice were tumour-free following treatment, but also that when re-injected with cancer cells 150 days after cure, they did not form new tumours. There was also an increase in the number of cells with an immunological memory.
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.