Immunotherapy, a novel form of cancer treatment that boosts a person’s own immune system to fight cancer cells, has revolutionized care for patients with melanoma and has helped them live significantly longer. People who respond well to immunotherapy tend to have long lasting responses; however, there are people who still end up having their disease come back. In addition, there are also side effects associated with immunotherapy that can be permanent and life-threatening. There are single drug immunotherapies and there are combination immunotherapies given for melanoma, each with a different risk profile for chances of side effects and a different likelihood of response.

Our goal is to characterize the patients here at our cancer center who have received immunotherapy as their first treatment for advanced stage melanoma. Our hypothesis is that patients who respond very well to immunotherapy will have long lasting responses regardless of the amount of immunotherapy they get after they have a good response. We aim to capture information regarding the type of immunotherapy they have gotten, how long they have been receiving the therapy for, any side effects they may have developed from the treatment, and whether their disease came back, either after discontinuing treatment or while they were on treatment. We will compare patients who have had their disease come back after treatment to those patients who did not to see if there are any differences in characteristics of their melanoma. We are also interested in exploring whether these patient’s original tumors contain any information about their immune cells that may help guide likelihood of having side effects to immunotherapy. This information will help us better understand how long we should be continuing these treatments for and balancing the risks of developing serious side effects in order to improve care for patients with melanoma.

Uveal melanoma is the most common cancer that arises inside the eye. Today, most patients are treated with plaque radiotherapy, a highly effective form of targeted radiation that saves the eye and controls the tumor. While this treatment is life-saving, many patients experience gradual and sometimes severe vision loss in the treated eye, which can affect daily activities, independence, and overall quality of life.

A loss of 15 or more letters on a standard eye chart represents a meaningful decline in vision that patients can notice in everyday tasks such as reading, driving, or recognizing faces. Although this level of vision loss is widely used in clinical trials and by regulatory agencies, little is known about when it typically occurs and which patients are at highest risk after treatment for ocular melanoma.

This project studies vision outcomes in a large group of 4,000 patients who were treated with plaque radiotherapy for uveal melanoma before the routine use of modern vision-protecting injections. By carefully analyzing long-term vision changes, we aim to understand how often significant vision loss occurs, how soon after treatment it develops, and how tumor size and treatment factors influence this risk.

The results of this study will help doctors provide clearer and more personalized information to patients at the time of diagnosis. It will also provide a critical comparison point for newer treatments designed to reduce vision loss after radiation therapy. Ultimately, this work supports the goal of not only saving patients’ lives but also preserving their vision and quality of life.

Melanoma is the fifth most common cancer and is the deadliest form of skin cancer. While new immunotherapies called “checkpoint inhibitors” have revolutionized treatment, only about 30% of patients experience long-lasting benefit. Many tumors create a hostile environment that shields cancer cells from the immune system by recruiting suppressive cells and exhausting the T cells that would otherwise attack the tumor.

We propose a novel combination approach using two existing treatments: an influenza (flu) vaccine injected directly into tumors and a drug that blocks a protein called BRD4. When flu vaccine is injected into tumors, it activates the immune system to go to the site of cancer cells. The BRD4-blocking drug removes the suppressive cells that normally protect the tumor and keeps T cells from becoming exhausted, allowing them to continue fighting.

Our research will test whether giving flu vaccine first, followed by the BRD4 drug, can reprogram the tumor environment to be allow the immune system to be more active and effectively clear cancer cells. We will measure tumor shrinkage, analyze the immune cells inside tumors, and determine whether this combination helps checkpoint inhibitors, a current class of medications used to treat melanoma, work better.

This approach is particularly promising because flu vaccines are already FDA-approved and widely available, and BRD4 inhibitors are being tested in cancer clinical trials. If successful, this combination could offer additional treatment options for melanoma patients who don’t respond to current immunotherapies, potentially providing a safe, accessible treatment strategy that could be rapidly translated to the clinic.

Immunotherapy has dramatically improved outcomes for many patients with advanced melanoma. These treatments work by helping the immune system recognize and attack cancer cells. However, not all patients benefit from immunotherapy, and some develop resistance. Understanding why this happens is critical to improving treatment outcomes.
Recent research has shown that gut bacteria can influence how well immunotherapy works in melanoma. Much less is known about the bacteria in the mouth and overall oral health, even though oral health problems are common and can affect inflammation and immune function throughout the body. Inflammation of the gums and disruptions in oral microbes have been linked to chronic inflammation and alterations of the immune system, which may impact how patients respond to immunotherapy.

This study will explore whether oral health, bacteria found in saliva, and bacteria found in stool are associated with how patients with melanoma respond to immunotherapy. Patients starting immunotherapy will be asked to provide saliva and stool samples before treatment begins and again during treatment. Participants will also complete short, validated surveys about their oral health and dietary habits. These samples will be analyzed using established laboratory methods to identify and compare bacterial patterns in the mouth and gut.

Information about treatment response and side effects will be obtained from the medical record. By comparing oral health measures and bacterial patterns with treatment outcomes, this study aims to identify early signals that may help explain why some patients respond better to immunotherapy than others.

The results will guide future research aimed at understanding how oral health and the microbiome influence cancer treatment and may ultimately lead to new strategies to improve immunotherapy effectiveness for patients with melanoma.