Researchers have identified a role for tertiary lymphoid structures (TLS) in maintaining an immune-responsive tumor microenvironment in patients with melanoma. The study was published on January 15, 2020 in Nature.
Tertiary lymphoid structures are lymphoid organs that form in non-lymphoid areas experiencing chronic inflammation, including tumors. Researchers examined 177 retrospective tissue samples from patients with melanoma and determined that the presence of TLS was associated with increased patient survival. In addition, they showed that T cells in tumors without TLS had dysfunctional molecular phenotypes that included increased expression of the immune checkpoint inhibitors TIM3 and PD-1 and decreased expression of the cell death regulator BCL-2. These changes in gene expression impair the ability of T cells to identify and destroy tumor cells.
The researchers also identified a gene signature associated with the presence of TLS in melanoma tumors using differential expression analysis. They found that the gene signature was associated with overall patient survival. Further, the signature was able to predict patient response to immunotherapy treatment; those with melanoma tumors expressing high levels of the TLS genes were significantly more likely to survive following treatment.
Based on these findings, the TLS gene signature could be a valuable tool for predicting response to immunotherapy. The study results may also lead to the development of new therapeutic strategies aimed at enhancing the formation and function of TLS in order to increase the efficacy of immune cells in the tumor microenvironment.