TIL Therapy Promising in Uveal Melanoma, Tool Predicts Responders

A certain clinical tool may help doctors determine which uveal melanomas will respond to TIL therapy.

Researchers have found a new strategy that may help uveal melanoma respond to conventional immunotherapy. The adoptive therapy, which involves growing immune T cells outside of the patient’s body and then reinfusing them, was recently explained in Nature Communications.

“The dogma was that uveal melanoma is a ‘cold’ cancer, meaning that T cells can’t get into these tumors,” senior author Dr. Udai Kammula, associate professor of surgery at Pitt and director of the Solid Tumor Cell Therapy Program at UPMC Hillman Cancer Center, said in a press release.

Uveal melanoma is a rare kind of cancer that occurs in the eye.

The National Cancer Institute reports that treatment options for the disease include surgery, active surveillance, radiation, photocoagulation and thermotherapy.

READ MORE: Treatments, Patient Characteristics Affect Uveal Melanoma Survival

‘Liberating’ T Cells from a Suppressive Tumor Environment

Kammula and his team analyzed samples from 100 uveal melanoma metastases collected from 84 patients. They found that most samples had immune T cells that were able to infiltrate the tumor. However, instead of killing the cancer cells, the T cells are then inactivated.

“We show that T cells are in fact infiltrating metastases and they’re getting activated. But they’re just sitting there in a dormant state because something in the tumor is suppressing them. Adoptive therapy allows us to rescue these cells from the suppressive tumor microenvironment and successfully treat some patients,” Kammula said.

The researchers then tried an outside-the-body method to counter the growth suppression of these T cells. The goal was to determine if the T cells were able to grow and reproduce outside of the tumor environment. This method is called TIL (tumor-infiltrating lymphocyte) therapy. The first of its kind was approved by the Food and Drug Administration earlier this year for the treatment of advanced melanoma.

“By liberating these cells from the suppressive environment and growing them in the lab, we can rescue their tumor-fighting capacity when infused back into the patient,” Kammula said.

Predicting Which Uveal Melanomas Will Respond to TIL Therapy

While this method may be promising, it will not work for everyone, according to Kammula. So, he and his team developed a clinical tool called the Uveal Melanoma Immunogenic Score (UMIS) to predict which patients with metastatic uveal melanoma may benefit from TIL therapy. UMIS analyzes the activity of more than 2,000 genes expressed by tumor, immune, and other cells in and around the cancer. Higher UMIS scores indicated that tumors had more potent TILs.

Patients with higher UMIS scores tended to have better tumor regression (decreased size of the cancer). Those with metastases scoring above 0.246 tended to have improved progression-free and overall survival, which describe the time patients live without disease worsening and the time patients live before death of any cause, respectively.

“If a patient’s UMIS level is below this threshold, we think that adoptive therapy is not appropriate. Using a biopsy to calculate a patient’s UMIS could help avoid futile therapies and unnecessarily subjecting patients to invasive operations,” said Kammula. “But the immune system is not static. UMIS offers a window into the tumor that could also help us find the optimal time to treat a patient with adoptive therapy, like picking a fruit when it’s at its ripest.”

Kammula and his team are continuing to study the UMIS scoring system and TIL therapy in a uveal melanoma trial. He also mentioned that he hopes to take the concepts learned in this study and apply them to other difficult-to-treat cancers.

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