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UT MD Anderson Research News
Researchers at The University of Texas MD Anderson Cancer Center have discovered that immunosuppressed patients with non-melanoma skin cancer are not missing the key cancer-fighting immune cells found in immunocompetent patients, but those cells – known as macrophages – have lost the ability to communicate effectively. This new understanding may help researchers develop new treatment approaches for these aggressive skin cancers.
The study, published today in Cell, was co-led by Moran Amit, M.D., Ph.D., assistant professor of Head and Neck Surgery; Kunal Rai, Ph.D., associate professor of Genomic Medicine; Frederico Gleber-Netto, D.D.S., Ph.D., assistant professor of Head and Neck Surgery; Priyadharsini Nagarajan, M.D., Ph.D., associate professor of Anatomic Pathology; and Michael Migden, M.D., professor of Dermatology.
“For years, treating these patients has been very challenging, even in the era of immunotherapy. The prevailing thought has long been that these patients simply have fewer of these important immune cells, but that is not what we saw,” Amit said. “We learned that the quality of the immune cells and their interactions may be just as important as the number of cells present. This is an important finding because these patients need better treatment options.”
Why is skin cancer more dangerous in immunosuppressed patients?
| Key Points: |
| Patients with weakened immune systems develop non-melanoma skin cancers that are more frequent, more aggressive, and more often lethal |
| Study finds these skin cancers are not devoid of immune cells, but the interactions between these cells are failing |
| The defect localizes to macrophages, which help regulate the antitumor immune response |
| Understanding the specific immune defects responsible may point to new treatment and intervention opportunities |
Non-melanoma skin cancer is the most common cancer in the U.S. People with weakened immune systems, including organ transplant recipients and those with certain blood cancers, are more likely to develop aggressive forms of the disease. Often, their immunosuppression excludes these patients from being treated with the immune checkpoint inhibitors that benefit other patients, leaving them no immunotherapy options.
What did the researchers learn?
In this study, the team analyzed tumors from 138 patients with non-melanoma skin cancer. Patients with weakened immune systems had shorter disease-free survival and a five-year overall survival rate of 33% compared to 68.8% for patients with normal immune function.
Macrophages are white blood cells that help coordinate the body’s immune response. When functioning normally, macrophages help T cells recognize and attack cancer. Single-cell analysis revealed that tumors in immunosuppressed patients had many of the same immune-cell types, but they were less effective at sending cancer-related signals to other cells. Additionally, they had reduced receptor diversity, suggesting that their ability to recognize cancer cells was more limited.
What’s next for this research?
Understanding exactly how the immune cells are altered could help researchers develop methods for preventing or reversing those changes, opening new therapeutic options for these patients. These findings also highlight the importance of innate immunity in shaping antitumor responses, which could lead researchers to test treatments to boost this innate immunity or improve immune cell communication within tumors.
“Now that we know the cells are there, it changes how we approach this problem,” Amit said. “We are now investigating efforts to boost the cells or help them recover their lost functionality. That’s a shift in how we approach this disease, but it could lead to promising new avenues of research for treatments.”
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This research was supported by the National Institutes of Health’s National Cancer Institute and National Institute of Craniofacial Research, the Cancer Prevention and Research Institute of Texas (CPRIT) and institutional funding from UT MD Anderson. For a full list of collaborating authors and their disclosures, read the full paper in Cell.
The prevailing thought has long been that these patients simply have fewer of these important immune cells, but that is not what we saw. We learned that the quality of the immune cells and their interactions may be just as important as the number of cells present.
Information source: UT MD Anderson Research News
