When a skin cancer patient has a weakened immune system, doctors have long assumed the problem was simple: not enough of the right immune cells to fight the disease. But new research from Houston, Texas is turning that assumption upside down.
Scientists at MD Anderson Cancer Center discovered that immunosuppressed patients with non-melanoma skin cancer actually have the same key cancer-fighting immune cells as other patients. The cells just cannot talk to each other properly. These immune cells, called macrophages, are white blood cells that help coordinate the body's defense system. Normally, macrophages help another type of immune cell called T cells recognize and attack cancer. In immunosuppressed patients, that communication line is broken.
The study analyzed tumors from 138 patients with non-melanoma skin cancer, the most common cancer in the United States. The results were striking: patients with weakened immune systems had a five-year survival rate of just 33%, compared to 68.8% for patients with normal immune function. This included organ transplant recipients and people with certain blood cancers.
"For years, treating these patients has been very challenging, even in the era of immunotherapy," said Dr. Moran Amit, one of the study's lead researchers and an assistant professor at MD Anderson. The prevailing belief was that these patients simply had fewer macrophages. "We learned that the quality of the immune cells and their interactions may be just as important as the number of cells present."
Using a technique called single-cell analysis, the team found that tumors in immunosuppressed patients contained many of the same immune cell types as other patients. But these cells were less effective at sending cancer-related signals to other cells and had reduced ability to recognize cancer cells overall.
The research, published in the journal Cell, was co-led by Dr. Kunal Rai, Dr. Frederico Gleber-Netto, Dr. Priyadharsini Nagarajan, and Dr. Michael Migden alongside Dr. Amit.
The findings could open new doors for treatment. Since the cells are present but just not functioning correctly, researchers can focus on ways to restore their ability to communicate or boost their activity. This is especially important because immunosuppressed patients often cannot use immune checkpoint inhibitors, the immunotherapy drugs that help other patients.
"Now that we know the cells are there, it changes how we approach this problem," Dr. Amit said. The team is now investigating ways to help macrophages recover their lost functionality. It is a shift in thinking that could lead to promising new treatments for one of the most difficult-to-treat groups of skin cancer patients.