3. Cancer immunotheray: the great hope

Although the role our defenses play in the fight against cancer has been known since the late 19^th century, it has only been in the last five years that immunotherapy has become the great hope for cancer.

Our immune system is always on the lookout for foreign bodies. When a tumor begins, its mutations make it different from the rest of our cells and our defenses fight to eliminate it. But at some point the body can fail, because the cancer looks for ways to avoid its defenses.

One of these ways is to cover itself in a sort of invisibility cloak. Tumors do this with a layer of molecules called PD-L1. When these molecules interact with the complementary ones in the defense system’s lymphocytes, they render them inactive. One of the most promising drugs is what is known as immune checkpoint inhibitors: antibodies that stop the tumor from being able to do this. They have been particularly effective in treating melanoma (the most aggressive type of skin cancer), and they also seem to have an effect on tumors like those in the lungs and kidneys. In large part due to this, cancer immunotherapy was named the scientific breakthrough of the year by the journal Science in 2013.

But there are other types of tumors that don’t seem to respond, and no one really knows why. The group led by Michael Karin, professor of Microbiology at the University of California, is studying possible reasons in prostate, liver and pancreatic tumors. “The immune system fights the cancer and some types of chemotherapy can help the body recognize it,” said Karin. This theory is based in part on the fact that chemotherapy kills many tumor cells and, in destroying them, causes many of their substances to be liberated, making it easier for the body’s defenses to find them. However, on occasion something paradoxical happens. As Karin explained, “It sounds unbelievable, but some B lymphocytes (the ones that produce antibodies) can inhibit the war the T lymphocytes (the ones responsible for coordinating the immune response) wage on the tumor after chemotherapy.” These rebel lymphocytes seem to act through the PD-L1 molecule (the invisibility cloak), so “A combination of chemotherapy and immunotherapy, if administered at the same time, could be helpful for this type of tumor,” he explained.

Another way of stimulating the immune system against cancer is through vaccines. Although they have shown promise for years now, only one has been approved for prostate cancer and its effectiveness is quite limited. But there are new strategies that seek to increase their power exponentially by designing fully personalized vaccines based on looking for the mutations in each tumor and determining which have the greatest probability of provoking a strong reaction from the defense system. This is the focus of the work of the group led by Sebastian Kreiter, director of the Immune Therapy Development Center (TRON) at Johannes Gutenberg University in Mainz, and their research has already led to a clinical trail on a personalized vaccine in melanoma patients.

And there is still another path in the approach to chemotherapy, which involves using oncolytic viruses. These viruses are harmless and selectively attack tumor cells. This is what the group led by Ramón Alemany, head of the ICO Virotherapy Center, is working on. “We want to fight tumors with viruses, but for the virus to also facilitate the work of the immune system,” said Alemany. It would be somewhat similar to the role of chemotherapy, which in destroying the tumor cells reveals them to the defense system. But it isn't easy, because in many cases the viruses don’t arrive in the right quantities and because the defense system tends to attack the virus more than the tumor itself. That’s why scientists are working on solutions. Some of them include incubating special forms of viruses that can hide from the immune system or inserting part of the tumor into the outer coating of the virus so the body’s defenses will attack both at once.

One way or another, the future seems to lie in good part down the path of immunotherapy, although not exclusively. Joaquín Arribas explained, “In many cases, cancer treatment will surely require a combination of immunotherapy and precision medicine with molecular targets.”