Cancer Immunity Can Be Outsourced, Using Healthy Donors

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The immune system of cancer patients fails to recognize aberrant cancer cells as foreign invaders. However, as researchers from the University of Oslo have observed, if grown in the presence of healthy donor cells, donor T cells can recognize cancer cells, which can be used as a potential guide for future cancer treatments.

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Cancer cells are like terrorists. Under normal circumstances our immune system has state-of-the-art surveilling capabilities and suspect cells are recognized and destroyed. Sometimes the guardians of our immune system are blinded, or the cancer cells blend in with the normal cells and are able to evade detection – thus hijacking our immune system and wreaking havoc.

There has been a paradigm shift in cancer research where it is now recognized that our body’s own immune system can be used to effectively recognize cancer cells, and use its own machinery to get past what's referred to as “immunological checkpoints” in order to mount a robust immune response. These checkpoints allow our bodies to guard against the threat of autoimmunity, such distinguishing malignant cells as foreign invaders versus “self-cells” that they need to avoid. Tumors express a variety of molecules on the cell surface, which scientists are hoping the immune system, will recognize and attack, once those inhibitory checkpoints are surpassed.

New research in cancer immunotherapy from the University of Norway, published in Science, discusses the inability to mount an immune response in individuals with a tumor can be overcome by utilizing donor immune cells instead. Mutations in DNA found in cancer cells trigger the immune system’s alarm allowing them to be discovered. But this does not always occur. However, when these same cancer cells are grown in the presence of a healthy donor’s immune cells this “borrowed immune system” allowed the cancer cells to be recognized as an aberration and killed.

The donor immune system is capable of seeing proteins that are expressed on cancer cell surfaces, known as “neoantigens.” These neoantigens are foreign protein fragments, or molecular tags, that identify them as being derived from mutant DNA. The T cells from the healthy donor’s immune system were able to recognize the neoantigens that the host’s immune system had missed.

The authors are using this finding as proof of concept that perhaps the specific cancer recognizing T cells can be isolated, and used to genetically modify the patient’s own T cells to do the same thing.

“In a way, our findings show that the immune response in cancer patients can be strengthened; there is more on the cancer cells that makes them foreign that we can exploit. One way we consider this is finding the right donor T cells to match these neo-antigens,” stated Ton Schumacher of the Netherlands Cancer Insititute, one of the authors of the study.  “The receptor that is used by these donor T-cells can then be used to genetically modify the patient’s own T cells so these will be able to detect the cancer cells.”

Though, much work still needs to be done before borrowing a healthy donor immune system can be used for treatment of cancer patients. What this research has shown is that the “outsourcing” of cancer immunity can be done, only the methods of how T cells are capable of recognizing cancer cells need to be further explored.