With current immunotherapy approaches, T-cells are mobilized against specific tumors and their genetic mutations.
Now, researchers at the University of California, San Francisco in San Fracisco, California, say it may be possible to go a step further and enhance immunotherapy by taking advantage of a tumor’s microenvironment. They have been studying antigen-presenting cells (APCs) within multiple tumor types and discovered that there are clear cut ‘good’ APCs and a much larger pool of ‘poor’ APCs.
The researchers have delineated the intratumoral dendritic cells population and identified CD103+ dendritic cells, which are extremely sparse and yet remarkably capable cytotoxic T cell (CTL) stimulators.1
The newly identified CD103+ dendritic cells appear to be dependent on IRF8, Zbtb46, and Batf3 transcription factors and generated by GM-CSF and FTL3L cytokines. It is hoped that it may be possible to manipulate their numbers for new cancer immunotherapies.
“We are taking a different tact,” said study investigator Matthew Krummel, PhD, who is a professor of pathology at the University of California, San Francisco. “When you undertake current immunotherapies, you are typically only throwing one molecular switch.
However, a tumor has a series of switches, so you have to throw a couple of them. Currently, we typically only know how to throw switches in T cells.”
Dr. Krummel and his colleagues believe they may have come up with a novel way of throwing more switches in additional cells of the immune response. They have shown that CD103+ dendritic cells in tumors are associated with better oncological outcomes and may have therapeutic potential.
The signature for antigen-presenting CD103+ dendritic cells was associated with significantly better clinical outcomes in head and neck cancers and in breast cancers.
Krummel and colleagues looked at 3,602 patient tumor samples representing 12 cancer types. The samples included 845 breast, 265 ovarian, 303 head and neck squamous, 122 bladder, 168 glioblastoma, 190 colon, 173 acute myeloid leukemia, 72 rectal, 355 lung adenocarcinoma, 259 lung squamous, 480 kidney, and 370 uterine cancers from a single data set by the Cancer Genome Atlas PanCancer working group.2
They found that the prevalence of CD103+ dendritic cells in tumors correlated with clinical outcomes. Patients who had the signature for CD103+ dendritic cells appeared to consistently have better overall survival (OS) than those with weak signatures.