The results of a recent clinical trial (NCT03743766) published in Cell might pave the way for significant advances in treating advanced melanoma , a serious form of skin cancer.
The study, led by University of Pittsburgh and UPMC Hillman Cancer Centers researchers, Anthony R. Cillo, John M. Kirkwood, Tullia C. Bruno, and Dario A.A. Vignali, with colleagues from Moffitt Cancer Center and Research Institute, Abramson Cancer Center, and the Washington School of Medicine in St. Louis, investigated how two promising cancer drugs, Relatlimab and Nivolumab, work both individually and together to treat advanced melanoma.
The combination boosted the immune system’s ability to recognize and attack cancer cells (cytotoxicity), even though some immune cells showed signs of being tired from fighting against the cancer cells (exhaustion).
How does it work?
The combination of Relatlimab plus Nivolumab enhances the cytotoxicity of a certain type of immune cells, called CD8+ T cells. CD8+ T cells are like the “soldiers” of your immune system. Their job is to find and destroy infected or cancerous cells. But after fighting cancer for a long time, these cells can become less functional or “exhausted” and start to express exhaustion proteins that act like brakes to slow down these soldiers. Relatlimab and Nivolumab block these exhaustion proteins to turn these cells back on, and when used together, they helped CD8+ T cells to do their job better by:
- Boosting Signaling: The combination makes CD8+ T cells better at receiving signals that tell them to attack cancer cells. It’s like giving these cells a louder, clearer message to target the bad guys.
- Enhancing Cytotoxicity: These CD8+ T cells become more effective at killing cancer cells, even if they still show some signs of being exhausted. This means they can fight harder and longer.
The study also revealed that certain proteins inside the CD8+ T cells, known as transcription factors, play a key role in how these cells respond to the treatment. Transcription factors are “master regulators” of the functions of cells, and understanding these proteins could help scientists develop more targeted therapies that could help the immune system recognize and destroy cancer cells more effectively in the future. This study revealed that several transcription factors, including PRDM1 and TOXI, have important roles in allowing the CD8+ T cells to respond to treatment.
This study offers hope that new treatments could boost the immune system to fight cancer, which could mean fewer side effects and better outcomes for people fighting advanced melanoma.
More on PRDM1 and TOX:
Researchers have found a groundbreaking way to help CD8+ T cells target cancer cells more precisely. This discovery involves the transcription factors PRDM1 and TOX. Previously, TOX was thought to govern CD8+ T cell exhaustion, but researchers found that after treatment Relatlimab and Nivolumab, TOX instead works to promote CD8+ T cell function. The transcription factor PRDM1 further supported the ability of CD8+ T cells to kill cancer by promoting development towards a “killer” state.
By understanding how TOX and PRDM1 work to promote immune cell-mediated killing of cancer, scientists hope to find new ways to make cancer cells visible and vulnerable to the immune system.
Why Is This Important?
This research is crucial because it opens doors to new cancer therapies. By understanding how these transcription factors govern immune cells, scientists can develop drugs or treatments that help the immune system recognize and destroy cancer cells more effectively. It’s like giving the immune system a better blueprint on how to defeat cancer.
