University of Texas MD Anderson Cancer Center (MD Anderson) researchers have created a new, pan-cancer, single-cell atlas to help elucidate the diversity of T cells and their states in tumor microenvironments.
The pan-cancer T-cell atlas integrates 27 single-cell RNA sequencing datasets, including 9 unique datasets from MD Anderson, covering 16 cancer types. Published recently in Nature Medicine, the study sheds light on the previously undescribed T-cell roles and relationships and their possible implications on the efficacy of immunotherapy.
A notable discovery: T cell response state
Cells in the T cell stress response state, or TSTR, can be thought of as “stressed out” cells that seem to be less effective at fighting cancer. The new T-cell atlas helped researchers identify and characterize TSTR cells as a unique group—distinct from other CD4+, CD8+, or exhausted T cell subsets.
Per the researchers, TSTR cells exhibit high heat shock gene expression and are seen at significantly higher fractions in both CD4+/CD8+ T cells following immune checkpoint blockade therapy—particularly in nonresponders.
“Investigating the mechanistic causes of stress response in T cells, understanding how these stressed T cells are induced in the tumor microenvironment, and learning how to stop or reverse this TSTR state could catalyze the development of more effective therapeutic strategies that may bring the benefit of immunotherapy to more cancer patients,” said corresponding author, Linghua Wang, MD, PhD, associate professor of genomic medicine at MD Anderson, in a recent press release.
In the study, the team described a total of 32 T-cell states and identified seven subpopulations within the CD4+ regulatory subset, five within the CD4+ follicular helper T cell population, and eight states among proliferating T cells.
“There are still many questions left to answer,” said Wang. “One of the limitations of this study is we don’t have the corresponding T cell receptor data for most of the datasets analyzed. We are not sure what triggers the TSTR state, and we don’t know from which T cell subset(s) they originate. It also is unclear whether these TSTR cells are specific to tumor cells and how they communicate with and influence other cells within the tumor microenvironment.”
These findings underscore the need to further investigate how T-cell states contribute to cancer progression and affect future therapies.