The most frequent kind of lung cancer in humans is non-small cell lung cancer (NSCLC). Immune checkpoint blockade (ICB) is a treatment for NSCLC patients that helps kill cancer cells by reviving a group of immune cells called T cells that have become “exhausted” and stopped acting.
Only approximately 35% of NSCLC patients react to ICB therapy, however. Stefani Spranger’s team at the Massachusetts Institute of Technology’s Department of Biology investigates the processes underlying this resistance in the hopes of developing new medicines to better treat NSCLC patients.
Resistance To Cancer Therapy Is Determined By Differences In T Cell
Cancers are of several types, and in almost every type, it is difficult to overcome this illness as mental trauma, and physical supports of patients are difficult to gain.
Hence for experts, it was necessary to find the prime cause, and the same has been detected among the T cells as per research. If these cells can be managed to have the effects of cancer removed, the cure for the same can be easier than ever before, resulting in saving many lives.
A team led by Spranger lab postdoc Brendan Horton revealed what causes T cells to be non-responsive in a recent study published on Oct. 29 in Science Immunology.
Scientists have long assumed that the environment within a tumour determines when T cells quit operating and get weary after being overstimulated or fighting a tumour for an extended period of time.
That’s why doctors use ICB to treat cancer: it can re-energize the tumour’s depleted T cells. However, according to Horton’s recent research, some ICB-resistant T cells quit operating before even entering the tumour. These T cells aren’t actually fatigued; rather, alterations in gene expression that occur early during T cell activation in lymph nodes cause them to become dysfunctional.
T cells develop into several functional states once activated, which are distinguished by their distinct gene expression patterns.
According to Spranger, the Howard S. and Linda B. Stern Career Development Professor, a member of the Koch Institute for Integrative Cancer Research, and the study’s senior author, the notion that the dysfunctional state that leads to ICB resistance arises before T cells enter the tumour is quite novel.
“We show that this is a pre-determined state and that T cells are already non-responsive to therapy before they enter the tumour,” she explains. As a result, ICB therapies that act by reviving fatigued T cells within the tumour are less likely to be effective, she argues.
This shows that combining ICB with other types of immunotherapy that target T cells in various ways could be a more effective way to assist the immune system in fighting this type of lung cancer.
Horton and his colleagues researched T cells in NSCLC mouse models to figure out why some cancers are resistant to ICB. To see if there were any variations between the T cells, the researchers sequenced messenger RNA from responsive and non-responsive T cells.
They employed a technology called Seq-Well, created in the lab of fellow Koch Institute member J. Christopher Love, the Raymond A. Koch Institute Frontier Research Program.
Once activated, CD8+ T lymphocytes are capable of recognizing and killing host tumour cells that carry the non-mutated self-peptide. Following activation with the altered form of the antigen, T cells that recognize a self-antigen are capable of destroying tumour cells expressing the self-antigen.
(1921) and Helen E. St.Laurent Professor of Chemical Engineering, as well as a study co-author. Spranger and Horton were able to acquire a very detailed look at the gene expression patterns of the T cells they were analyzed using this approach, which allows for fast gene expression profiling of single cells.
