T cell exhaustion- new insights


Researchers have just discovered a gene that exhausts T cells, which might provide new avenues for developing more potent immunotherapies.

White blood cells that fight cancer need to be robust, especially T lymphocytes or T cells, a subset of white blood cells that participates in the immune system’s battle against cancer cells. However, during this conflict, T cells may become worn out. A gene that appears to contribute to this tiredness has just been discovered by researchers.

Since around 20 years ago, T lymphocyte fatigue has been recognised as a concern. T cells develop a state of weariness and lose some of their effectiveness after repeated exposure to tumour cells; even while they continue to detect the cancer cells as enemies, they generate less chemicals to destroy them. Additionally, they are unable to mature into memory T cells, which are crucial for sustaining the immunological response.

As a result, the study team worked to comprehend the processes that result in T cell depletion. They created a model based on human tumour cells and created worn-out lymphocytes that resembled those present in patient tumours. The CRISPR/Cas9 technique was then used by the scientists to individually inactivate a number of genes and assess the results.

They were able to find a gene that controls T cell fatigue as a result. When this gene, known as SNX9, is inactivated, T cells continue to operate even after spending a prolonged time near a tumour. These results are quite encouraging because there aren’t many targets to stop T cell fatigue, and the majority of studies to describe such targets have been carried out in mouse cells.

Journal article: Trefny, M.P., et al., 2023. Deletion of SNX9 alleviates CD8 T cell exhaustion for effective cellular cancer immunotherapy. Nature Communications.

Summary by Stefan Botha

International Union of Immunological SocietiesUniversity of South AfricaInstitute of Infectious Disease and Molecular MedicineElizabeth Glazer Pediatric Aids Foundation