T-cell fraction: a quantitative technique to predict risk of melanoma recurrence?

Researchers from Brigham and Women’s Hospital (MA, USA) report a novel quantitative technique based on measuring the fraction of T cells in a tumor sample that could be used to predict disease progression in individuals with primary melanoma. The retrospective study, published in Nature Cancer, reports that primary melanoma patients with a lower T-cell fraction (less than 20%) are 2.5 times more likely to have cancer metastasize than those with a higher T-cell fraction (greater than 20%).

For the majority of patients, primary melanomas begin as a small pigmented spot on the skin. In some cased this can be treated through the removal of the lesion, however melanoma can recur and spread. Analysis of the removed lesion can provide insight into the likelihood of cancer recurrence, however, the techniques currently used to analyze these lesions have remained largely unchanged despite advances in molecular diagnostics and the available treatment options. Lesion analysis often involves measuring lesion thickness, with thinner lesions being associated to better patient outcomes.

“This is a simple, elegant test. It’s quantitative rather than subjective, and it may be able to add value to predictions about disease progression.” – David Kupper, Co-author (Brigham and Women’s Hospital)

New immunotherapy treatments such as immune checkpoint inhibitors, which can reawaken T cells to mount an immune response against cancer cells, have dramatically changed outcomes in patients where melanomas have spread. However, due to the limited ability of current techniques to predict which patients are at greatest risk of disease progression, it is a challenge to tailor treatment accordingly.

In the report, a team of researchers present a new quantitative technique based on measuring the fraction of cells in a tumor that are T cells – the T-cell fraction – that could be used to make more accurate predictions about which primary melanomas are likely to recur and spread.

The team aimed to identify quantifiable features of T cells that could be used to predict recurrence in patients following primary melanoma removal. By analyzing the T cell repertoire of tumor samples from patients whose primary melanoma progressed to metastatic disease and those whose did not, the team identified that T cell fraction could be a powerful independent predictor of which patients’ disease would progress. In patient samples where lesion thickness was the same, T-cell fraction successfully identified which patients were more likely to have metastatic disease.

To perform the high-throughput DNA sequencing of tumor samples in this study, the team made use of Adaptive Biotechnologies (WA, USA) proprietary immune profiling platform, which is currently not available for clinical use. As the study is retrospective, additional research with patients whose outcomes are unknown is required to further validate the test.

Corresponding author, David Kupper, MD and Chair of the Department of Dermatology (Brigham and Women’s Hospital) explained: “This is a simple, elegant test. It’s quantitative rather than subjective, and it may be able to add value to predictions about disease progression. In the future, such a test could help us tailor treatment; patients with high T-cell fraction may further benefit from checkpoint inhibitor therapy, while low T-cell fraction patients may need additional intervention.”

Sources: Pruessmann W et al. Molecular analysis of primary melanoma T cells identifies patients at risk for metastatic recurrence Nat. Cancer doi:10.1038/s43018-019-0019-5 (Epub ahead of print)(2020); www.eurekalert.org/pub_releases/2020-01/bawh-ntp011620.php