Macrophage communication failure key in NMSC

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 macrophages found in immunocompetent patients. Instead, those cells have lost the ability to communicate effectively. The researchers say this new understanding may help researchers develop new treatment approaches for these aggressive skin cancers.

The study was published in Cell.

Moran Amit, MD, PhD. Photo courtesy UT MD Anderson

“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,” said co-lead author Moran Amit, MD, PhD, in a press release. “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.”

The authors note that people with weakened immune systems, including organ transplant recipients and those with certain blood cancers, are more likely to develop aggressive forms of non-melanoma skin cancer. Often, their immunosuppression excludes these patients from being treated with the immune checkpoint inhibitors that benefit other patients, leaving them no immunotherapy options.

In this study, the team analyzed tumours 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.

Single-cell analysis revealed that tumours 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.

The authors say that understanding exactly how the macrophages are altered could help researchers develop methods for preventing or reversing those changes, opening new therapeutic options for these patients. They say their 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 tumours.

“Now that we know the cells are there, it changes how we approach this problem,” Dr. 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.”