Study: Blood-borne MDSC suppress immune system

Cancer cells have developed a multitude of mechanisms that allow them to evade destruction by the immune system. One of these escape mechanisms involves an immune cell called myeloid-derived suppressor cells (MDSC).

A study led by Sharon Evans, Ph.D., Professor of Oncology and Immunology at Roswell Park Cancer Institute, provided new insight into how MDSCs enable tumor cells to circumvent immune attack and offer the potential for improving cancer immunotherapy. The research has been published in the journal eLife.

“This investigation could lead to the identification of novel therapeutic targets that bolster the body's protective mechanisms against the development of metastatic disease,” Dr. Evans said. “These new insights may allow us to address a pressing challenge faced by physicians: how to determine which cancer patients are most likely to benefit from T lymphocyte-based immune-therapeutics.”

Tumor cells cause extensive expansion of MDSC, which are associated with poor prognosis in patients with various types of cancer. Dr. Evans and colleagues used a state-of-the-art microscopy system to visualize T lymphocytes, part of the immune system that kills cancer cells.

They discovered that MDSC can blunt the immune reaction to cancer by preventing the ability of T lymphocytes to enter lymph nodes, important sites where the immune response to invading cancers becomes ramped up. Myeloid-derived suppressor cells accomplish this by removing a molecule (L-selectin) from the surface of T lymphocytes that is essential for cellular trafficking into lymph nodes. As a result, the protective immune response to cancer is severely compromised.

One finding of this investigation was that MDSC can act directly on T cells to limit their widespread trafficking to lymph nodes. This subversive activity of MDSC was not restricted only to T lymphocytes but included B lymphocytes, which are responsible for generating protective antibodies against tumor cells. The team's research established for the first time that B lymphocytes are also a target of MDSC in cancer.

“Because these immune-suppressive myeloid cells were found to act at long distances to prevent the activation of the T lymphocyte response to tumors, this research reinforces the important message that routine profiling of the cellular constituents of tissues does not always provide the whole picture in cancer,” said Dr. Amy Ku, a student in the Department of Immunology at Roswell Park.