Invasive procedures to biopsy tissue from cancer-tainted organs could be replaced by simply taking samples from a tiny decoy implanted just beneath the skin, according to University of Michigan researchers. These devices attract cancer cells traveling through the body and can even pick up signs that cancer is preparing to spread, before cancer cells arrive, the scientists said.
The team published its study (“Metastatic conditioning of myeloid cells at a subcutaneous synthetic niche reflects disease progression and predicts therapeutic outcomes”) in Cancer Research.
“Monitoring metastatic events in distal tissues is challenged by their sporadic occurrence in obscure and inaccessible locations within these vital organs. A synthetic biomaterial scaffold can function as a synthetic metastatic niche to reveal the nature of these distal sites. These implanted scaffolds promote tissue ingrowth, which upon cancer initiation is transformed into a metastatic niche that captures aggressive circulating tumor cells,” the investigators wrote.
“We hypothesized that immune cell phenotypes at synthetic niches reflect the immunosuppressive conditioning within a host that contributes to metastatic cell recruitment and can identify disease progression and response to therapy. We analyzed the expression of 632 immune-centric genes in tissue biopsied from implants at weekly intervals following inoculation.
“Specific immune populations within implants were then analyzed by single-cell RNA-seq. Dynamic gene expression profiles in innate cells, such as myeloid-derived suppressor cells, macrophages, and dendritic cells, suggest the development of an immunosuppressive microenvironment. These dynamics in immune phenotypes at implants was analogous to that in the diseased lung and had distinct dynamics compared to blood leukocytes. Following a therapeutic excision of the primary tumor, longitudinal tracking of immune phenotypes at the implant in individual mice showed an initial response to therapy, which over time differentiated recurrence versus survival. Collectively, the microenvironment at the synthetic niche acts as a sentinel by reflecting both progression and regression of disease.”
“Biopsying an organ like the lung is a risky procedure that’s done only sparingly,” said Lonnie Shea, PhD, the William and Valerie Hall chair of biomedical engineering at the University of Michigan. “We place these scaffolds right under the skin, so they’re readily accessible.”
The ease of access would also allow doctors to monitor the effectiveness of cancer treatments closer to real-time, he added.
Working with mice, biopsies of the scaffold allowed researchers to analyze 635 genes present in the captured cancer cells. From these genes, the team identified ten that could predict whether a mouse was healthy, if it had a cancer that had not begun to spread yet, or if a cancer was present and had begun to spread. They could do that all without the need for an invasive biopsy of an organ.
The gene expression obtained at the scaffold had distinct patterns relative to cells from the blood, which are obtained via a liquid biopsy. These differences highlight that the tissue in these traps provides unique information that correlates with disease progression, noted Shea.
The researchers have demonstrated that the synthetic scaffolds work with multiple types of cancers in mice, including pancreatic cancer. They work by luring immune cells, which, in turn, attract cancer cells.
“When we started off, the idea was that we would biopsy the scaffold and look for tumor cells that had followed the immune cells there,” Shea said. “But we realized that by analyzing the immune cells that gather first, we can detect the cancer before it’s spreading.”
In treating cancer, early detection is key.
“Currently, early signs of metastasis can be difficult to detect,” said Jacqueline Jeruss, MD, an associate professor of surgery and biomedical engineering and a co-author of the study. “Imaging may be done once a patient experiences symptoms, but that implies the number of cancer cells may already be substantial. Improved detection methods are needed to identify metastasis at a point when targeted treatments can have a significant beneficial impact on slowing disease progression.”
The immune cells allowed researchers to identify whether treatments were effective in the mice and which subjects were sensitive or resistant to treatment.
The decoy’s ability to draw immune and cancer cells can also bolster the treatment itself. In previous research, the devices demonstrated an ability to slow the growth of metastatic breast cancer tumors in mice, by reducing the number of cancer cells that can reach those tumors.
In the future, Shea envisions that the scaffolds could be outfitted with sensors and Bluetooth technology that could deliver information in real-time without the need for a biopsy.
