Immune System’s ’First Responders’ Are New Focus in Cancer Fight, Pioneered by Harvard’s Merad
BOSTON – A Harvard Medical School researcher is spearheading a radical shift in cancer treatment, focusing on harnessing the power of macrophages – immune cells often dismissed as simply “cleanup crews” – to actively fight tumors. Miriam Merad, director of the Institute for Immunological Science at Harvard, believes these cells, traditionally viewed as part of the immune system’s later-stage response, can be reprogrammed to recognize and destroy cancer cells, offering a potential breakthrough in a field frequently enough focused on T-cells.
For decades, cancer immunotherapy has largely centered on boosting T-cells, the immune system’s targeted assassins. However, many patients don’t respond to these therapies, and even those who do can develop resistance. Merad’s work suggests macrophages, the immune system’s “first responders” and most abundant white blood cell, hold a key to overcoming these limitations. This approach could broaden the reach of immunotherapy to a wider patient population and possibly offer more durable responses,impacting the lives of the over 1.9 million Americans diagnosed with cancer each year.
Merad’s research, building on years of immunological study, demonstrates that macrophages aren’t simply passive scavengers removing dead cells.Thay exist on a spectrum, from pro-inflammatory cells that promote healing to those that actively suppress the immune response – a characteristic tumors exploit to evade detection. Her team is developing strategies to “re-educate” macrophages,shifting them from tumor supporters to tumor killers.
“We’ve been overlooking a major player in the tumor microenvironment,” Merad explained in a recent interview. “Macrophages are incredibly plastic. We can actually change their fate and direct them to attack the cancer.”
The approach involves identifying the signals that dictate macrophage behavior and then manipulating those signals using antibodies or small molecule drugs. Early studies, detailed in publications like Cell and Nature, have shown promising results in preclinical models of various cancers, including breast, lung, and pancreatic cancer. Merad’s lab has identified specific macrophage subtypes that infiltrate tumors and,surprisingly,found that some of these cells already possess anti-cancer activity but are suppressed by the tumor environment.
Several companies are now racing to translate Merad’s findings into clinical therapies. Merad herself is a co-founder of Immunai, a biotech company utilizing spatial transcriptomics to map the immune landscape within tumors and identify macrophage-targeted therapies. Other firms, including large pharmaceutical companies, are also exploring macrophage-based immunotherapies.
Beyond cancer, the potential applications of Merad’s work extend to other diseases driven by inflammation. researchers are investigating macrophages’ role in 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.