Patients with non-Hodgkin’s lymphoma show better chances of survival if they have a diverse variety of T-cells, are diverse, according to recent research from the University of Queensland, Australia.
These findings may lead to the development of personalized immunotherapies to help patients who have failed to respond to current treatments.
The study, “The T-cell Receptor Repertoire Influences the Tumor Microenvironment and Is Associated with Survival in Aggressive B-cell Lymphoma,” was published in the journal Clinical Cancer Research.
T-cells are key cells of our immune system responsible for fighting infections and attacking cancer cells. The activation of T-cells against foreign or dangerous cells relies on their cell surface — specifically, on the so-called T-cell receptor (TCR). Previous studies have shown that a diverse repertoire of TCRs is crucial for the ability of T-cells to fight persistent infections. This means that diversity in the TCR leads to diverse T-cells with different capacities to fight infections.
While this link has been shown in infections, whether the same is true in human lymphomas has been unknown.
Researchers from the University of Queensland tackled this question and analyzed thoroughly the sequence of TCRs in 92 patients with diffuse large B-cell lymphoma (DLBCL), the most common type of fast-growing non-Hodgkin’s lymphoma, who received treatment with conventional (non-checkpoint blockade) therapy.
“The study was unique in that we were able to get the code for every one of the 2,500 or so T-cells from biopsies from a large group of patients with diffuse large B-cell lymphoma (DLBCL),” Dr. Colm Keane, the study’s first author, said in a press release.
They compared the TCR diversity from T-cells extracted from 12 non-diseased, normal lymph node tissues with those from the same lymph nodes of DLBCL patients.
When compared to T-cells from healthy lymph nodes, researchers observed that the TCR diversity of DLBCL was extremely reduced. In fact, they detected one highly dominant type of TCR associated with a four-year overall survival rate of below 60%, while patients with fewer of this particular TCR exhibited 79.8%. A single dominant TCR was also predicted to incur an inferior four-year progression-free survival rate of 46.6%, while more diverse TCRs were linked to four-year overall survival rates of 72.6%.
Overall, these results show that the T-cells in aggressive B-cell lymphomas are much less diverse than those in non-diseased lymph nodes, and that this loss of diversity is associated with poorer outcomes.
Now, researchers are “working to find which types of T-cells are associated with the best outcomes for lymphoma patients.”
They “hope then to be able to produce those in the laboratory and give them back to the patient to improve their response and chances of survival.”