HomeScience and ResearchScientific ResearchThis New T Cell Map is Revealing a Hidden Biology of Cancer...

This New T Cell Map is Revealing a Hidden Biology of Cancer We’ve Never Seen Before

Published on

The new research “provides the opportunity to see things that aren’t visible when studying a single type of cancer or even a handful of cancer types.”

A new study led by researchers from The University of Texas MD Anderson Cancer Center, and recently published in Nature Medicine, offers a profound understanding of the extensive range of T cell variations and their intricate relationships and functions within the complex tumor microenvironment. This study brings a fresh perspective to comprehend the effectiveness of immunotherapy in treating cancer.

The researchers have developed a comprehensive single-cell T-cell atlas that encompasses data from 27 separate single-cell RNA sequencing datasets, including nine distinctive datasets from MD Anderson. These datasets encompass 16 different types of cancer. This atlas represents the most detailed depiction to date of the diverse T cell populations within the tumor microenvironment.

It highlights how the phenotypic states of T cells, along with the relative proportions of each state, significantly impact the efficacy of immunotherapy and the likelihood of potential adverse effects.

“This kind of large dataset and comprehensive pan-cancer analysis provides the opportunity to see things that aren’t visible when studying a single type of cancer or even a handful of cancer types,” points out corresponding author Linghua Wang.

The author hopes “these high-resolution maps, including the thoroughly characterized T cell states, are valuable resources for facilitating future T cell studies and biomarker discovery.”

One significant finding from this study reveals a previously unidentified state in T cells known as the T cell stress response (TSTR). In earlier investigations involving single-cell analysis, these particular T cells were often disregarded or considered artifacts resulting from tissue dissociation. However, leveraging the extensive dataset available, the researchers successfully identified these cells as a distinct and unique group, separate from other subsets of CD4+ or CD8+ T cells. They also validated the existence of these cells in their native environment using various spatial profiling techniques.

TSTR cells can be likened to T cells that are under considerable stress. Similar to how stressed individuals may experience reduced effectiveness in their job, TSTR cells appear to be less efficient in combatting cancer. Although both TSTR cells and exhausted T cells may exhibit dysfunctional behavior, TSTR cells follow a distinct differentiation pathway that differs from the trajectory of exhausted T cells.

A new T cell state linked to immunotherapy resistance
A new T cell state linked to immunotherapy resistance

Key features of TSTR cells include heightened expression of heat shock genes. Importantly, these cells are found in significantly higher proportions among both CD4+ and CD8+ T cells following immune checkpoint blockade therapy, particularly in individuals who do not respond favorably to the treatment. This indicates that TSTR cells might contribute to resistance against immunotherapy. The identification of this novel T cell state deepens our understanding of the intricate biology underlying cancer and presents a potential target for future therapeutic interventions.

“The fact that these TSTR cells are found in many different types of tumors opens up a whole new world of possibilities that could have high translational potential,” explains Wang. “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.”

This research also emphasizes the significance of comprehensive and extensive datasets in the field of oncology. The development of this pan-cancer T cell atlas showcases the immense potential of utilizing big data to unravel the intricate landscape of T cells present in tumors. In this study, the team identified a total of 32 distinct T cell states, along with seven subpopulations within the CD4+ regulatory subset, five within the CD4+ follicular helper T cell population, and eight states among proliferating T cells.

These discoveries shed light on the vast diversity of T cell states within the tumor microenvironment, highlighting the importance of further investigating their role in disease progression and response to immunotherapy. It is crucial to gain a deeper understanding of how these different states of T cells contribute to the overall dynamics of cancer and the effectiveness of immunotherapeutic approaches.

“There are still many questions left to answer,” Wang adds. “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.”

The research team has made their T-cell atlas available to the broader scientific community through the Single-Cell Research Portal, an interactive and user-friendly web platform. This portal, created by the team, allows researchers, both internal and external, to easily visualize and explore the atlas, even without prior expertise in bioinformatics.

Additionally, the team has developed a tool called TCellMap, which assists researchers in annotating T cells within their own datasets. By aligning their data with the high-resolution T cell maps generated by this study, researchers can automatically annotate their T cells. Wang expressed optimism that these resources will be valuable to scientists who wish to conduct comprehensive analyses of T cells. It is anticipated that such analyses will lead to new discoveries and ultimately enhance strategies for T cell therapy.

Source: 10.1038/s41591-023-02371-y

Image Credit: Yunhe Liu, Ph.D., The University of Texas MD Anderson Cancer Center

Latest articles

Here’s How and When Mount Everest-sized ‘Devil Comet’ Can Be Seen With Naked Eye

Mount Everest sized Comet 12P/Pons-Brooks, also known as "devil comet" which is making its...

Something Fascinating Happened When a Giant Quantum Vortex was Created in Superfluid Helium

Scientists created a giant swirling vortex within superfluid helium that is chilled to the...

The Science of Middle-aged Brain and the Best Thing You Can Do to Keep it Healthy, Revealed

Middle age: It is an important period in brain aging, characterized by unique biological...

Science Shock: Salmon’s Food Choices Better at Reducing Risk of Heart Disease and Stroke

Salmon: Rich in Health Benefits, Yet May Offer Less Nutritional Value - This is...

More like this

Here’s How and When Mount Everest-sized ‘Devil Comet’ Can Be Seen With Naked Eye

Mount Everest sized Comet 12P/Pons-Brooks, also known as "devil comet" which is making its...

Something Fascinating Happened When a Giant Quantum Vortex was Created in Superfluid Helium

Scientists created a giant swirling vortex within superfluid helium that is chilled to the...

The Science of Middle-aged Brain and the Best Thing You Can Do to Keep it Healthy, Revealed

Middle age: It is an important period in brain aging, characterized by unique biological...