A team of scientists from the Massachusetts Institute of Technology have recently conducted a study regarding cancer immunotherapy. This field of science is dedicated to stimulating the body’s own immune system to detect and fight cancer cells the moment they begin to form.
What the study revealed is remarkable. It appears that researchers have now discovered a new possible way to eliminate tumor cells and treat cancer.
T cell studies
Under optimal conditions, the body produces T cells meant to identify and attack infected cells, such as tumors. But for most cancer patients, researchers observe that T cells become inactive as soon as they enter the environment of a tumor. Today, scientists are trying to find solutions to help treating patients, by activating T cells directly in order to trigger an immune response.
Through their new study, the MIT team found out that a specific group of dendritic cells are able to make T cells active again, in a very peculiar way. Dendritic cells are very important for the immune system, especially regarding tumor cells.
According to the study, this particular subset of dendritic cells appears to have the ability to disguise themselves into proteins which can only be found on tumor cells, which then triggers a strong immune response from T cells. Indeed, when coming across these supposedly infected cells, they start fighting the tumors.
As a consequence, the results of the study suggest that stimulating this very specific population of dendritic cells might be one of the answers to help treat some types of cancer.
The senior author of the study, Stefani Spranger, member of MIT’s Koch Institute for Integrative Cancer Research has led the whole project. Ellen Duong, Postdoctoral Scholar who graduated from the MIT Biology Department in 2021, is the lead author of the paper published on November 9th, 2021 in the online journal Immunity.
Spontaneous regression
T cells are a key part of cancer immunotherapy. They are meant to fight and eliminate tumors as soon as they start to form, thanks to their ability to detect cancerous proteins produced from the very beginning of their development. But in many cases, tumors release chemical signals which deactivate the T cells, leading to the growth of cancer cells.
Over the past few years, dendritic cells have been identified as helpers which can activate T cells, allowing them to fight tumors. But the main issue the scientists are facing is that this category of dendritic cells is a fairly large one. This study was mainly meant to determine as clearly as possible which types of dendritic cells trigger T cell responses, during the process of tumor elimination.
Before conducting clinical trials on mice, the MIT researchers decided to compare two types of tumors and their development.
They found out that a particular tumor cell line from a muscle tumor has shown to spontaneously regress, meaning that T cells remain active in the elimination of cancerous cells.
They compared that regressive tumor cell line with other cancer cells from colon carcinoma which are known to grow rapidly in the body. And it appears that the T cell immune response rapidly becomes inactive, and the tumor can easily grow larger without being stopped.
But why would one regress and not the other? The answer relies on the dendritic cell subsets present in these two different tumors.
Dendritic cells’ main role is to pick up debris from cancer or infected cells and show them to T cells, which will then detect the infection or tumor. DC1 cells were known to be the best type of dendritic cells to interact with T cells and fight tumors, but it appears that they are not required for tumor regression specifically. Researchers recently discovered an activation state of DC2 cells, a subgroup of dendritic cells which is involved in the regression of tumors, by activating T cells.
According to the study, these DC2 cells act differently from dendritic cells in general. Indeed, they don’t ingest cellular debris, but instead, they take up proteins coming directly from the tumor and display them on their surfaces. When T cells come across these supposedly infected cells, they strongly activate and start eliminating cancer cells.
To go further, the MIT team discovered that DC2 cells activation is triggered by type I interferon, a signaling molecule usually produced as part of the immune response.
The clinical trials revealed that these dendritic cells were present in colon and melanoma growing tumors, but they were not activated properly until type I interferon was injected. From that point, the dendritic cells started stimulating T cells to attack infected cells.
A targeted use
According to Dr Spranger, using interferon to treat every type of cancer cells doesn’t seem to be the correct way to treat patients, as it can have extensive side effects. The results of the study suggest that it would be better to use interferon on targeted tumor cells or to make these cells produce type I interferon themselves by injecting a particular drug.
In most cases, tumor cells naturally produce type I interferon. But the amount is so little that it’s not enough to activate dendritic cells which then revitalize T cells.
The MIT team is now investigating what amount of this interferon is needed to cause a strong T cell response to tumors. And it’s not an easy task to handle. Indeed, too much interferon could be dangerous and affect cells instead of activating them.
Dr Spranger and the MIT researchers now must understand and analyze the various ways our immune system responds when type I interferon is involved, which can either be a way to help treat cancer cells or it can become toxic to cells.
This study was funded and supported by different Cancer Research Institutions and Associations, including the Koch Institute Support (core) Grant from the National Cancer Institute, a National Institutes of Health Predoctoral Training Grant, a David H. Koch Graduate Fellowship, and the Pew-Stewart Fellowship.
