What makes some immune cells better at killing melanoma

New research in Nature identifies the properties of antitumor T cells, suggesting ways to boost T cell function in cancer

A healthy T cell. (Credit: NIAID)
A healthy T cell. (Credit: NIAID)

T cells rely on surface proteins called T cell receptors (TCRs) to bind to and destroy viruses, cancer cells, and other invaders in the body. T cells that infiltrate tumors, however, can have varied, sometimes ineffective responses. How the molecular structure and function of TCRs correlates with T cell behavior is not fully understood. 

In a new study published in Nature, Giacomo Oliveira, associated researcher and institute member Catherine Wu, and colleagues at the Dana-Farber Cancer Institute and the Cancer Program at the Broad Institute of MIT and Harvard take an in-depth look at the relationship between TCRs and T cell phenotypes. Using single cell RNA (scRNAseq) sequencing and TCR sequencing (scTCRseq) of CD8+ T cells, coupled with the detection of surface proteins, the researchers set out to study the transcriptomic and molecular profiles of melanoma tumor-invading T cells and their TCRs. They found that most T cells with tumor-specific TCRs bore the molecular signs of "exhaustion," a state of decreased function following chronic antigen exposure. Higher circulating levels of these tumor-invading, exhausted T cells in the blood correlated with persistent disease. These findings highlight the importance of restoring normal T cell function for a productive, effective immune response in cancer therapies.

In the video presentation above, Oliveira describes the research that led to the identification of the properties of antitumor T cells and highlights how such findings can pave the road to the development of novel therapeutic strategies that aim at generating T cells with potent antitumor TCRs and functional cell states.


Paper(s) cited

Oliveira G, et al. Phenotype, specificity and avidity of antitumour CD8+ T cells in melanoma. Nature. Published online July 21, 2021. DOI: 10.1038/s41586-021-03704-y.