Preventing tumors shedding their identifying proteins allows immune system to attack

Histological analysis (Fontana-Masson staining) of lung tissue demonstrated an apparent reduction in the number and size of metastases in mice that were treated with the MICA antibody (representative of five mice). 

A team of researchers have found that introducing an antibody into a cancerous mouse model prevented the escape of ligands from a tumor surface allowing natural killer cells to attack. In their paper published, the group describes their technique and how well it worked. A researcher offers an overview of the work done by the team in a Perspective piece in the same journal issue and also gives an overview of immunotherapy research in general.

Prior research has shown that one of the reasons the immune system has trouble recognizing tumors as a threat is the their tendency to shed proteins that the immune system uses to identify them. In this new effort, the researchers focused on MICA and MICB, proteins that are produced by tumors and wind up on their exposed surfaces, which the immune system would normally be able to identify. But before that can happen, the tumor actually produces an enzyme that separates the proteins from the tumor surface—essentially shedding them and preventing the immune system from using them as a signal to go on the offensive. In this new effort, the researchers looked into whether there might be a way to prevent tumors from shedding such proteins, thereby allowing the immune system to do its work.

After some searching, the team settled on an antibody called mAb 7C6—they found that when applied to mouse models with lung cancer and melanoma, the antibody caused levels of both MICA and MICB to increase on tumor surfaces, suggesting that the tumor had been unsuccessful in shedding them. Furthermore, they also found that killer immune cells were then alerted to the tumor and attacked it, which, the researchers report, resulted in a reduced tumor load.

The technique,the author notes, is one of many that are being developed to help the immune system fight tumors, rather than attacking tumors directly via medical interventions. Such therapies, it is believed, will have fewer undesirable side-effects. 

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