Ocular Melanoma News 2025 Part One discussed research that will predict tumor metastasis and a treatment using tebentafusp that helps immune cells recognize melanoma cells. There are other potential treatments for ocular melanoma being developed. One in particular deals with learning why ocular melanoma doesn’t respond to immunotherapy and how that can be changed.
Immunotherapy is a type of cancer treatment that utilizes a person’s immune system to fight cancer. A good example of this is skin cancer, which responds to immune checkpoint inhibitor drugs. The same can’t be said for ocular melanoma and no one knew why, until recently.
Researchers at the University of Pittsburgh Medical Center (UPMC) Hillman Cancer Center investigated what prevents ocular melanoma from from responding to immunotherapy. Led by Udai Kammula, M.D., associate professor of surgery at UPMC and director of the Solid Tumor Cell Therapy Program at UPMC Hillman Cancer Center, scientists extracted 19 tumors from ocular melanoma patients and grew T cells—a type of white blood cell that helps the immune system fight disease—in the lab. They then infused these cells back into the ocular melanoma and 35 percent of the patients had partial or complete regression of their cancer. While this therapy worked for these particular patients, it didn’t answer the question of why immune checkpoint inhibitors didn’t treat this disease.
Kammula and his colleagues were able to find the answer in the repository of uveal melanoma samples, corresponding tissues, and clinical information that his lab has been working on for the past decade. They studied 100 metastases from 84 patients and learned that over half of the tumors had T cells. When they did single cell RNA sequencing on close to 100,000 cells from six metastases to measure gene expression, they found that the tumor-infiltrating lymphocytes (TILs) in some tumors were activated and able to attack tumor cells. The trouble was that the TILs weren’t multiplying in large enough numbers to combat the tumor effectively.
Researchers discovered that the tumor microenvironment was suppressing the TILs, Once scientists removed these cells out the tumor and grow them in the lab, they are able to fight the tumor when infused back into the patient.
TIL therapy doesn’t work for everyone. To predict who will benefit and who won’t, Kammula and lead author Shravan Leonard-Murali, M.D., a postdoctoral fellow in the lab, developed a clinical tool called Uveal Melanoma Immunogenic Score (UMIS). This is a measure of the tumor’s activity across more than 2,000 genes expressed in the tumor microenvironment. The score ranges from 0.114 to 0.347 across 100 metastases, with higher values signifying tumors with more potent TILs. Researchers found that patients with higher UMIS scores had better tumor regression. This biomarker could predict who could respond well to treatment, allowing for more personalized therapies while avoiding therapies that didn’t work. The lab is now studying UMIS in a TIL therapy clinical trial for patients with metastatic ocular melanoma.
Speaking of which, research shows what is possible when it comes to the treatment of ocular melanoma. Work at Oregon Health & Science University on circulating hybrid cells in the blood provides clues about disease state and metastasis, which can be one day be used as a diagnostic biomarker. Memorial Sloan Kettering Cancer Center’s work on tebentafusp, showed promise in helping patients with this disease live longer. Lastly, research at UPMC Hillman Cancer Center studies on TIL therapy may help unlock immunotherapy options for those with ocular melanoma. These and other research projects offer hope to ocular melanoma patients that eye removal isn’t inevitable and the disease isn’t an automatic death sentence.
Sources:
https://www.cancer.org/cancer/managing-cancer/treatment-types/immunotherapy.html
https://www.upmc.com/media/news/041624-deadly-eye-cancer
https://my.clevelandclinic.org/health/body/24630-t-cells