Subverting Tumor Associated Macrophages in Order to Attack Cancer

Potential cancer therapies that can address many types of cancer should be a primary focus of the cancer research community. There are far too many varieties of cancer to do otherwise if the goal is rapid progress towards the control of cancer. In this early stage research, researchers report on an approach to using immune cells hijacked by cancerous tissue as a way to attack the cancer. This could in principle be applied to numerous types of cancer:

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.

Researchers have now 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. Using a bioinformatics approach, the researchers found that the most likely culprit was a small family of microRNAs, called Let-7. This offers a more specific target: blocking Let-7 microRNAs may help instruct the TAMs to stimulate anti-tumor immunity. Interestingly, the researchers observed that reprogramming TAMs also stops cancer cells from leaving the primary tumor. This could mean that the approach can also prevent tumor metastasis, the most threatening aspect of cancer. Moreover, the researchers found that the re-educated TAMs could enhance the anti-tumoral efficacy of certain cancer immunotherapies, some of which are already approved for patients. However, more work is needed to translate all these findings to actual therapies, especially since there is currently no way to block the Let-7 microRNAs selectively in TAMs. But researchers are now working to design drugs that can target the Let-7 microRNAs specifically in the TAMs.

Link: http://actu.epfl.ch/news/reclaiming-the-immune-system-s-assault-on-tumors/

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