Cancer cells have a tendency of hijacking human immune cells in an effort to avoid destruction by the immune system, but scientists are quickly responding to these defense mechanisms. A recent study resulted in unveiling of novel cancer mechanisms that scientists are hopeful will soon lead to new, more successful immunotherapy technologies.
Myeloid-derived suppressor cells (MDSCs) are the unlucky immune cells that fall under the spell of some types of cancer. Tumor cells actually trigger the massive expansion of the MDSC population, making high levels of these immune cells found in the bloodstream a marker of a poor prognosis for cancer patients.
The hijacking works for cancer cells because MDSCs can prevent T lymphocytes from entering the lymph nodes, where these effector cells of the immune system are supposed to receive their “training” for the specific cancer mission at hand. MDSCs do so by removing an important molecule from the T cell surface: L-selectin. The molecule is critical for the transportation of T cells to the lymph nodes. No L-selectin on the T cell surface, and the immune system is left severely impaired in the fight against cancer.
In their study observing T cells, a team from the Roswell Park Cancer Institute saw that MDSCs can act directly on T cells, a finding that was particularly surprising due to the rapid movement of cells circulating in blood.
"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," said explained first author Amy Ku, an MD/PhD student at the Roswell Park Cancer Institute.
Another surprising finding was that MDSCs act on B cells as well; this was the first time that B cells had be identified in addition to T cells as a target of tumor-controlled MDSCs.
In this scenario, the best answer might not be using chemicals to directly target the tumor cells, although that might be a supplementary option. The solution is instead to prevent tumor cells from manipulating MDSCs to inhibit the immune system in the first place, by “healing” the compromised T cells in some way and returning them to the circulation and the fight against the growing tumor.
“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,” explained leader of the study and senior author Sharon Evans, PhD.
Evans’ study was recently published in the journal eLife.
Source: Roswell Park Cancer Institute
