Role for immune cells in cancer’s ability to evade immunotherapy

Tumor cells cause extensive expansion of MDSCs, 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, the professional killers of cancer cells within the arsenal of the immune system. They discovered that MDSCs 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. MDSCs accomplish this by removing a molecule known as 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.

Given the rapid movement of cells within the circulation, one of the most surprising findings of this investigation was that MDSCs can act directly on T cells within fast-flowing blood to limit their widespread trafficking to lymph nodes. This subversive activity of MDSCs 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 MDSCs in cancer.

"This investigation could lead to the identification of novel therapeutic targets that bolster the body's protective mechanisms against the development of metastatic disease," says Dr. Evans, senior author of the new study. "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."

"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 within tissues does not always provide the whole picture in cancer," adds the paper's first author, Amy Ku, MD/PhD student in the Department of Immunology at Roswell Park.

This research was supported, in part, by grants from the National Institutes of Health (project nos. R01CA79765, R01AI082039, T32CA085183, T32CA108456, R01CA203348, R01CA115880, R01CA140622, R01CA172105, R01GMO21248, R50CA211108, P30CA016056), the University at Buffalo Mark Diamond Research Fund, the Jennifer Linscott Tietgen Family Foundation, and the Breast Cancer Coalition of Rochester.