When cancer patients go into remission, many are plagued by the fear that the cancer will return years later and by the possibility that it will metastasize and affect new areas of the body. One of the biggest questions in immuno-oncology is if and how immunotherapy can prevent such latent metastasis. Research has shown that our immune systems have the ability to detect and kill a number of metastatic cancer cells, but it seems that some of these cells are able to escape detection. Since these escaping cells have not yet resulted in full-blown relapse, they prove exceedingly hard to study. However, scientists at Memorial Sloan Kettering in New York have recently developed a model that could help explain how latent metastasis occurs and suggest new avenues for prevention.
The Reality of Cancer Recurrence
Once patients go into remission, the possibility of cancer returning is always present. Recently, Oncology Times reported on a man who was free from cancer for 29 years after his kidney cancer went into remission—until the cancer unexpectedly returned. Such a long interval is unusual, but recurrence is not. About one in four women with HER2-positive breast cancer will experience recurrence, and about half of lung cancer patients will have their cancer return at some point. Furthermore, patients who receive an organ from a donor who
previously had cancer sometimes develop the disease, especially when given heavy doses of immune suppressants to prevent rejection.
Tumor cells shed cancerous cells in the body from the time that they form until they are surgically removed. While the majority of these abnormal cells die, the few that do not are what cause cancer recurrence. The problem that oncologists face is the fact that such cells can go into hiding and avoid attack from the immune system, which allows cancer to flare up elsewhere in the body. Understanding this latency process will prove extremely important to achieving real, lasting cancer cures in the future. The researchers at Memorial Sloan Kettering have taken the first step toward preventing recurrence by identifying at least part of the mechanism that allows cancer cells to avoid detection by the immune system.
The Preliminary Memorial Sloan Kettering Research
Scientists have a hard time identifying latent cancer cells that might be present in the body, before the question of how they hide is even considered. The phenomenon of latent metastasis has been documented thoroughly, but few options for studying causes exist. The Memorial Sloan Kettering team approached the question by collecting tumor cells from people with early-stage breast and lung cancers and labeling them with a fluorescent tag. Then, the cells were injected into mice and the researchers waited several months.
After this period, most of the transplanted cells had died, but a few survived. With the fluorescent tags, researchers were able to find them hiding in the lungs and kidneys. In the study, these surviving cells were called “latency competent cancer cells.” Once the cells were collected, researchers were able to look at what allowed them to survive unharmed.
The team found that these unique cells behaved much like stem cells, which can divide at certain times to help repair tissues. Because of this stem-like behavior, the latent cells could divide and travel to distant organs. Researchers also found that some of the cells produced a protein called a WNT inhibitor that blocks cell division and essentially induces a state of suspended animation. The slowed growth plays a large role in the cells’ ability to evade the immune system.
The Initial Model for Latent Metastasis
Researchers hypothesized that because the latent cancer cells did not divide, they were able to avoid detection from natural killer cells that patrol the body. Natural killer cells look for things outside the ordinary, such as the molecules created by cancer cells dividing. If the cells do not divide, then natural killer cells will ignore them.
Furthermore, chemotherapies target dividing cells, so the non-dividing latent cells are not affected by these treatments. These two facts can help explain how a few cells survive in the body. Over time, these cells can develop other mutations that may also help them escape immune patrol and create new tumors in the future.
Importantly, the model developed by the Memorial Sloan Kettering team points to some potential treatment options to prevent the formation of latent tumors. One effective strategy would involve inducing latent cells to produce the molecules that natural killer cells look for, so that they can no longer avoid the normal immune response. Currently, the team that created this model is collaborating with immunologists to further study the cells and identify ways of forcing such expression. The team hopes that new therapies could be available for commercial use within a decade.
Such treatments could have a major impact on cancer treatment by reducing the chance of recurrence.