Thanks to immunotherapy treatments, many patients achieve longer survival and long-term remission. But not all patients benefit from treatment, and researchers are working to better understand why some cancers respond while others continue to grow.
AMRF-funded researcher Lewis Newland, a recipient of a 2024 Post Graduate Scholar Grant, is investigating how the immune system responds when melanoma spreads to the lymph nodes, often the first site of metastasis in melanoma and an important factor in determining patient outcomes.
Lymph nodes are a critical part of the body’s immune system. They act as communication hubs where immune cells coordinate responses against infections and diseases, including cancer. However, when melanoma spreads to these sites, the relationship between the cancer and the immune system becomes much more complex.
One promising treatment approach is Adoptive T Cell Therapy (ACT). This therapy involves collecting or generating tumour-fighting T cells, activating them in the laboratory, and then transferring them back into the body to target cancer cells.
“With funding from AMRF, we were able to perform cutting-edge experiments to determine how the transferred T cells differ between metastasis that are successfully controlled to those where therapy fails. Not only have these funded experiments provided important insight into ACT responses to lymph node metastases, they have also led us to identify genes that we may be able to target to improve treatment.” – Dr Lewis Newland
While ACT has achieved remarkable success in some blood cancers and shown encouraging results in melanoma, researchers still do not fully understand how effective it is against melanoma that has spread to the lymph nodes.
To address this question, Lewis and his research team developed a novel laboratory model that closely mimics the way melanoma progresses and spreads in patients. Using this model, they were able to track how lymph node metastases responded following treatment with tumour-specific T cells.
The results were curious. Some lymph node metastases were successfully controlled by the transferred T cells and remained stable for weeks. Others, however, were able to resist treatment and continue growing despite the presence of these cancer-fighting immune cells.
With support from AMRF, Lewis used advanced single-cell RNA sequencing technology to examine the individual T cells involved in these different outcomes. This cutting-edge approach allowed the team to analyse the genetic activity of thousands of immune cells and identify important differences between successful and unsuccessful treatment responses.
The research revealed distinct populations of T cells that were associated with either tumour control or treatment resistance. By mapping how these immune cells changed over time, the team was also able to identify biological pathways and genes that may influence whether immunotherapy succeeds or fails.
These findings provide new insights into how melanoma interacts with the immune system within lymph nodes and why some metastases are able to evade immune attack.
The study has also identified potential new targets that could be used to improve the effectiveness of adoptive T cell therapy in the future. The next stage of the research will investigate whether modifying these pathways can enhance the ability of T cells to eliminate melanoma and whether these discoveries could eventually be translated into improved treatments for patients.
While there is still more to learn, studies like this bring us one step closer to more effective treatments and better outcomes for people living with melanoma. This project demonstrates the value of supporting Australia’s next generation of melanoma researchers as they work to answer some of the disease’s most challenging questions.
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