Dogs turn out to be much better models for the study of prostate cancer than mice, the animal typically used in the laboratory for this type of research. In one study, researchers were able to explore the pathways used by cancer to evade the immune system and identify an antibody that dramatically improves survival rates.
Prostate cancer is the most common malignancy in men, with approximately 1.2 million new cases and 359,000 deaths recorded annually worldwide. Androgen suppression therapy is a first-line treatment. Alone or in combination with chemotherapy, it is indeed initially effective in about 80 to 90% of advanced cases. However, the disease can progress to a resistant form, reducing the chances of survival. Also, new treatment options allowing a durable control of the disease are always necessary.
Cancer uses a range of tricks to hide from the immune system. According to a recent study, some cells are particularly capable of entering a state of dormancy to avoid destruction by chemotherapy. This sneaky maneuver could explain why some people respond poorly to these treatments. It could also explain why some cancers seem to "come back" suddenly after several years.
Another trick is to turn certain immune system cells against itself. Specifically, the regulatory T cells (Tregs) play a key role in identifying these immune cells by marking them so our bodies don't mistakenly attack them, as happens in autoimmune diseases. However, it appears that cancer cells seem to be capable of hijacking this mechanism by tricking regulatory T cells into marking them to prevent them from being attacked. Thanks to this sleight of hand, the disease can eventually grow and spread.
High levels of Tregs have been detected in several types of cancers. Also, some researchers are working on possible antibody-based treatments capable of reducing the levels of these cells in the desired region.
As part of recent work, researchers from the University of Tokyo have studied this technique in dogs, whose prostate has a structure similar to that of humans. Note that all dogs involved in this study had developed naturally occurring cancer.
For this work, the team first analyzed the degree to which prostate cancer had been infiltrated by regulatory T cells (Tregs) and how this occurs. was producing. Using RNA sequencing and protein analysis, she then noticed that these Tregs seemed to be attracted to the tumor in greater amounts when a protein called CCL17 bound to a receptor called CCR4.
On this observation, the researchers then administered an antibody called mogamulizumab capable of blocking this receptor. Result:dogs who received this treatment were found to have lower levels of circulating Tregs and survived longer with few adverse side effects compared to the control group.
These works are obviously promising, even if the road is still long. However, there are good reasons for hope. Analyzes performed on human patients with prostate cancer have indeed also revealed elevated levels of Tregs infiltrating the tumor expressing CCR4. Additionally, mogamulizumab has already been approved for use in humans by most health authorities as a possible treatment for a range of other diseases.
