Defeating Cancer's Defenses against the Immune System

The most exciting advances in cancer treatment these days involve helping the body's own defenses fight cancer cells. I wrote last year about one such treatment, which involves genetically reprogramming T-cells. Now there is buzz about another approach:

For more than a century, researchers were puzzled by the uncanny ability of cancer cells to evade the immune system. They knew cancer cells were grotesquely abnormal and should be killed by white blood cells. In the laboratory, in Petri dishes, white blood cells could go on the attack against cancer cells. Why, then, could cancers survive in the body?

The answer, when it finally came in recent years, arrived with a bonus: a way to thwart a cancer’s strategy. Researchers discovered that cancers wrap themselves in an invisible protective shield. And they learned that they could break into that shield with the right drugs. When the immune system is free to attack, cancers can shrink and stop growing or even disappear in lucky patients with the best responses. It may not matter which type of cancer a person has. What matters is letting the immune system do its job.

So far this approach is wildly unpredictable, seeming to cure some patients completely and doing nothing for others. Nobody knows why. But certainly there is real promise here. More detail on how these drugs work:

The story of the new cancer treatments started with the discovery of how cancers evade attacks. It turned out that they use the body’s own brakes, which normally shut down the immune system after it has done its job killing virus-infected cells. One braking system, for example, uses a molecule, PD-1, on the surface of T-cells of the immune system. If a target cell has molecules known as PD-L1 or PD-L2 on its surface, the T-cell cannot attack it. So some cancer cells drape themselves in those molecules. The effect, when T-cells are near, is like turning off a light switch. The T-cells just shut down. Cancers that do not use PD-L1 or PD-L2 are thought to use other similar systems, just starting to be explored. Body systems have a lot of redundancy to tamp down immune attacks. But for now, the PD system showed researchers how cancer cells can evade destruction. “That is what has been realized in the past few years,” said Ira Mellman, vice president of research oncology at Genentech. “Tumor cells are making use of this brake.” The discovery led to an idea: Perhaps a drug that covered up any of those PD molecules, on the cancer cells or on white blood cells, would allow the immune system to do its job.

And so it seems to be.

The hard-core science types have always said that defeating cancer requires understanding it at the molecular level. They have used this logic to justify hundreds of billions of dollars in spending by the world's governments, creating an enormous biomedical research complex. So far, the results in terms of extending life have been modest. But maybe as we really come to understand how cells work, and how to manipulate them, we will finally create effective treatments.

On a completely different note, reporter Gina Kolata spoke to one of the patients whose treatment had been successful. He had been through hellish treatments for lung cancer -- surgery, radiation, chemotherapy --but his cancer returned. He tried one type of experimental drug, and it did no good. Then he tried a PD-1 inhibitor, and his tumors shrank dramatically and have not come back. Did he credit biomedical science, or his doctor, or the government's health spending? No. He said, "The Lord wanted me to be alive, and I am alive."