Research spotlight: Identifying genes to prolong an anti-tumor immune response

How would you summarize your study for a lay audience?

We set out to identify genes that are commonly expressed in CD8⁺ T cells, killer immune cells that can drive anti-tumor immunity, across many types of human cancers. Our goal was to uncover new therapeutic targets, which could inform novel treatment strategies that could benefit many patients. To do this, we developed a novel mathematical method that can be applied to data from many types of cancers.

What knowledge gaps does your study help to fill?

We know the presence fof CD8⁺ T cells is essential for attacking and destroying cancer cells. If we can prolong the survival of these cells, then they can work longer to destroy cancer cells.

How did you conduct your study?

We created and implemented a novel mathematical method that can identify patterns in data and be applied to analyze diverse datasets across multiple human cancers to reveal shared or unique gene programs. We applied this formula to study 33,161 CD8⁺ T cells fro 132 patients with seven different types of cancer. We thus identified 72 genes that we commonly expressed in chronically activated CD8⁺ T cells across these cancers. We found that one of these genes, CXCR6, can support the survival of CD8⁺ T cells by promoting CD28 signaling. 

What are the implications?

Because the mathematical method we developed can be applied to analyze diverse datasets across multiple human cancers to uncover shared or unique gene programs, we can identify common, as well as unique, targets for cancer therapeutics, Our findings can help inform targets for broadly active cancer therapies, 

What are the next steps?

Using the same method, we will identify unique targets for specific cancer types and continue to test additional genes within our 72 “pan-cancer” candidates for therapeutic translation and application.

Authorship: In addition to Anderson, additional Brigham and Women’s Hospital authors include Katherine Tooley, Giulia Escobar, S. Harsha Krovi, Davide Mangani, Gitanjali Dandekar, Hanning Cheng, Conner Lambden, Rajesh Krishnan

Funding: This work was supported by funds provided by the President’s Scholar Award and grants from the National Institutes of Health (R01CA187975; P01CA236749) the Klarman Cell Observatory at the Broad Institute, and Howard Hughes Medical Institute.

Paper cited: Tooley, K et al. “Pan-cancer mapping of single CD8⁺ T cells profiles reveals a TCF1:CXCR6 axis regulating CD28 co-stimulation and anti-tumor immunity.” Cell Reports Medicine DOI: https:doi.org/10.1016/j.xcrm.2024.101640