Miriam Merad’s fascination with macrophages began when she looked into the lungs of a cancer patient she’d just lost during her residency. He developed a rare allergy to the chemotherapy, and died rapidly. The case still haunts her. “When you have a patient dying of a treatment that you gave, you never forget that,” she said. “It’s very present.”
The medical team figured the tumor plus the allergy led to his death. But Merad couldn’t shake how extreme the allergic reaction was and insisted on an autopsy. Within hours, she had lung tissue. “We did what we call a warm autopsy. I looked at it and, I mean, these lesions,” she recalled, holding her hands up. “The cancer was gone. There were no cancer cells, and it was full of macrophages.”
The sight stunned her. Macrophages, immune cells often called the “gatekeepers” of the immune response, were known to often be immunosuppressive in the context of cancer, dampening the body’s natural ability to fight it. But in this case, Merad thought they must have been connected to a massive inflammatory response that had destroyed the tumor, but also the lung. If she could understand that inflammatory process, she thought, then maybe it could be harnessed for powerful new therapies.
“I became convinced that, somehow, these macrophages could be extremely potent,” she said.
Since the inception of cancer immunotherapy, most of the field has focused on T cells, the immune system’s specialized killers and its primary tool against tumors. Immunotherapies have transformed cancer treatment in the last decade, with Merck’s Keytruda, engineered cell therapies like CAR-T, and other T cell-targeting drugs extending lives and even completely eliminating tumors in some cases. But many patients don’t respond or eventually stop responding to these therapies.
Merad and a growing number of researchers believe macrophages are the key to making immunotherapies work for more people. They are seeing hope from early clinical trial data that macrophage targeted therapies might be able to synergize with T cell therapies and enhance immunotherapy for cancer. Biologists are starting to dive into how these cells may be central to aging, which may lead to new treatments for diseases like dementia and even new ways to help people age better and improve their health span. Companies and academic labs are also experimenting with macrophages to help control inflammatory and autoimmune diseases like lupus.
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