A newly discovered type of immune cells in tumors is associated with less severe cancer outcomes in humans and may have therapeutic potential, according to a new study in the journal Cancer Cell (October 16, 2014).
Molecules associated with these cells could be the focus of new immunotherapies that are more precisely targeted than current immunotherapies now in clinical trials, according to study lead Matthew Krummel, PhD, a professor of pathology at the University of California, San Francisco (UCSF).
The presence of these cells may be the reason current immunotherapies aimed at boosting T lymphocyte responses are so effective, the UCSF researchers concluded.
Matthew Krummel, PhD. Image courtesy of UCSF.In the study, the researchers depleted the population of these rare cells in mice and demonstrated that the immune system was subsequently unable to control tumors, even when the mice were given immunotherapeutic treatments. The study included 3,600 human tumors of 12 types and also mouse experiments.
"We found a rare cell type, present in most tumors -- but very sparsely -- that confers immunity and, thus, assists in immune rejection of the tumor," Krummel said in a statement.
Tumors are able to grow and metastasize partly because they subvert the immune system. Cancers prevent the activation of T lymphocytes within the immune system that specifically target tumor molecules that the body recognizes as abnormal.
Immune cells known as antigen-presenting cells need to activate T lymphocytes to trigger them to attack, but in cancer, cells called tumor-associated macrophages tell T lymphocytes to remain dormant and also enable the development of blood vessels that feed the growing tumor.
However, the distinct, rare population of cells newly identified by Krummel's team persists in trying to activate tumor-targeting T lymphocytes, apparently with enough success despite their scarcity to make a difference in cancer outcomes. Krummel calls the cells antigen-presenting CD103+ dendritic cells, and they make up less than 1% of all antigen-presenting cells, he said.
The researchers found specific molecules on the cells that serve as a signature for their identification, and molecules that might be targeted to boost the cells' power to activate T lymphocytes.
"Patients who have the signature of these cells live consistently longer than those with weak signatures," Krummel said. "These antigen-presenting CD103+ dendritic cells are an important but previously unrecognized ally in immunity to cancer, and we believe that we can learn to manipulate their numbers for new cancer immunotherapies."
The researchers have identified proteins that they plan to target to enhance the good cells, and, conversely, they hope to treat molecules on the surface of the bad cells as targets to eliminate those cells.
The association of the signature for antigen-presenting CD103+ dendritic cells with better outcomes was especially strong in head and neck cancers and in breast cancers, the researchers found.
The strength of the association between the CD103+ cell signature and cancer outcomes raises the prospect that researchers might even be able to detect cancer early via an immune response. "We want to find genes that are only present in immune cells in cancer and not in people without cancer," Krummel said.
The National Institutes of Health provided the major funding for the study.
