Triggering the Body’s Defenses to Fight Cancer

Arming the immune system to help fight cancer
image edited by F. Kaskais

Experiments once considered crazy are now helping scientists attack tumors.


One day in 2010, when oncologist Paul Muizelaar operated on a patient with glioblastoma—a brain tumor infamous for its deathly toll—he did something shocking. First, he cut the skull open and carved out as much of the tumor as he could. But before he replaced the piece of skull to close the wound, he soaked it in a solution containing Enterobacter aerogenes,1 bacteria found in feces. For the next month, the patient lay in a coma in an intensive care unit battling the bacteria he was infected with—and then one day a scan of his brain no longer showed the distinctive signature of glioblastoma. Instead, it showed an abscess, which, given the situation, Muizelaar deemed a positive development. “A brain abscess can be treated, a glioblastoma cannot,” he later told the New Yorker. Trying it, he thought, was worth the chance. He had done this only as a means of last resort in a couple of hopeless cases—but ultimately, his patients still passed away, which led to a scandal that forced him to retire.

Muizelaar’s approach may sound beyond outrageous, but it wasn’t entirely crazy. For over 200 years medics have known that infections, particularly those accompanied by fevers, can have a strange and shocking effect on cancers: Sometimes they wipe the tumors out. The empirical evidence for these hard-to-believe cures has been documented in medical literature, dating back to the 1700s. In the 19th century, some doctors tried treating cancer patients by deliberately infecting them with live bacterial pathogens. Sometimes it worked, sometimes the patients died. Injecting people with dead bacteria worked better and, in fact, saved lives, at least in some cancers. The problem was that it didn’t work consistently and repeatedly so it never became an established treatment paradigm. Moreover, no one could explain how the method worked and what it did. Doctors speculated that infections somehow revved up the body’s defenses, but even in the early 20th century, they had no means of elucidating the mysterious force that devoured the tumor.

RESCUE REPROGRAMMING: Tumor-associated macrophages (green) can help cancer cells (red) grow, but they can also be reprogrammed to kill them. The image on the left is a petri dish with mouse tumor-associated macrophages and breast tumor cells 48 hours after mixing the cells together; in this case, the macrophages don’t kill the cancer cells. But when CSHL postdoc Lijuan Sun added interferon-gamma and MPLA (an immune booster) to the petri dish, the macrophages were reprogrammed and began eating the tumor cells. The image on the right shows the results 48 hours later.Cold Spring Harbor Laboratory

Today we know that this mystery lies in the complex interplay of cancers and the immune system, says Mikala Egeblad at Cold Spring Harbor Laboratory, who studies the tumultuous interactions between cancers and the organisms they grow in. We know that cancers have an uncanny ability to pull wool over the eyes of the immune system’s cells—not only by hiding from them, but even co-opting them to help themselves flourish. “Tumors are dysregulated organs,” says Egeblad—and they dysregulate the environment around them too. They cause a lot of turmoil and havoc wherever they take hold. Called the tumor microenvironment, that “battleground” is teeming with various microscopic players that cancers corrupt into unwitting allies.

“Our immune system is trying to protect us from various threats, including cancer,” says Karin Pelka at Gladstone-UCSF Institute of Genomic Immunology who studies the cellular interactions that shape immune responses. “But cancer mutates in ways that it evolves to evade the immune system. So there’s a constant battle going on.”

In these dysregulated, messy ecosystems, infections may indeed serve as a force that rights the wrongs. They could reboot the body’s normal defense mechanisms, making the immune system see the enemy. However, deliberately infecting cancer patients with bacterial pathogens faces a major obstacle. It will never pass FDA approval because subjecting people—who are already gravely ill and fighting for their lives—to yet another health threat is unethical, reckless, and risky. And yet new directions in cancer treatment draw on the immune system kickstart idea, albeit in a different way. Moreover, some of the immunological approaches to cancer treatments have graduated from clinical trials to actual clinics.

He had done this only as a means of last resort in a couple of hopeless cases.

Today, medicine has better methods for resetting the body’s idle defenses that don’t involve infecting patients with pathogens. And there are different ways to do it, says Pelka. One of them employs the so-called oncolytic viruses—genetically engineered or naturally existing viruses that infect only tumor cells, multiply inside, then burst them open, invading more cells…


F. Kaskais Web Guru

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