Researchers Identified A Gene That Leads To T Cell Exhaustion, A Discovery That May Pave The Way For More Effective Cancer Immunotherapies
T lymphocytes, also known as T cells, play a critical role in our immune system’s battle against cancer cells. However, during this fight, it is not uncommon for T cells to become exhausted.
So, overcoming T cell exhaustion to improve immunotherapy has become a key focal point in cancer research.
Just recently, scientists from the University of Basel in Switzerland have also added to this growing body of research with a breakthrough discovery.
They identified a gene that seemingly contributes to the exhaustion of T cells– a finding that may pave the way for more successful immunotherapies.
T cells’ fading ability to kill cancer cells, the phenomenon commonly referred to as “exhaustion,” has been a recognized problem for approximately two decades. Once T cells endure chronic exposure to cancerous tumor cells, they eventually enter an exhausted state that makes them less effective.
So, while the T cells continue recognizing hostile tumor cells, they still produce fewer substances that can eliminate cancer. Moreover, T cells stop developing into memory T cells– which are another key component for supporting immune system response.
In turn, T cell exhaustion adversely impacts immunotherapies’ effectiveness– since these therapies are reliant on stimulating the human body’s intrinsic immune defense against cancer.
“This also applies to cell therapies to tackle cancer. Even if ‘new’ T cells are injected into patients, the exhaustion remains a problem,” said Alfred Zippelius, the study’s co-author.
The researchers were thus inspired to gain a deeper understanding of the mechanisms that lead to T cell exhaustion.
Gorodenkoff – stock.adobe.com – illustrative purposes only, not the actual person
First, the team created a model based on tumor cells. Then, they produced exhausted lymphocytes– which are similar to the T cells found in patient tumors. Afterward, the researchers analyzed various genes by individually inactivating them. This inactivation was accomplished using a gene editing process known as CRISPR/Cas9.
In doing so, the team successfully identified one gene– known as SNX9– that is responsible for regulating T cell exhaustion. They found that when the gene is inactivated, T cells remain functional– regardless of whether they are located near a tumor for a longer period of time.
In other words, the SNX9 gene seemingly increases short-term immune response– which can be very important in instances when each hour counts in the fight against diseases.
“In the case of our experiment, however, suppressing the SNX9 gene enabled finer adjustment of immune cell activity by reducing excessive stimulation signals. The T cells’ activity was, therefore, conserved over a longer period,” explained Marcel Trefny, the study’s lead author.
Finally, the study also revealed how instead of just dying after completing their jobs, the T cells more frequently developed into memory T cells.
According to Zippelius, this discovery of SNX9’s role may pave the way for more efficient immunotherapies in the future. In the meantime, though, clinical tests regarding the therapeutic application of this gene inactivation must be conducted to determine whether the absence of SNX9 leads to adverse effects.
To read the study’s complete findings, which have since been published in Nature Communications, visit the link here.
If true crime defines your free time, this is for you: join Chip Chick’s True Crime Tribe
Sign up for Chip Chick’s newsletter and get stories like this delivered to your inbox.
More About:Science