A New Weapon Against Advanced Melanoma: How Doctors Are Using Your Own Immune Cells to Fight Cancer

A groundbreaking immunotherapy called tumor-infiltrating lymphocyte (TIL) therapy is offering new hope to patients with advanced melanoma who have exhausted conventional treatment options. Ochsner MD Anderson Cancer Center in New Orleans recently became the first institution in Louisiana to provide this cutting-edge treatment, marking a significant milestone in personalized cancer care.

What Is TIL Therapy and How Does It Work?

TIL therapy represents a fundamentally different approach to fighting cancer by harnessing your body's natural defenses. Unlike traditional chemotherapy or radiation, this immunotherapy uses your own immune cells—specifically lymphocytes extracted directly from your tumor—to attack cancer cells.

The process involves several carefully orchestrated steps:

• Tumor Cell Extraction: Surgeons remove a small piece of the cancerous tumor and isolate lymphocytes, which are immune cells naturally present within the tumor that have already learned to recognize cancer.
• Laboratory Expansion: These lymphocytes are activated and multiplied in a laboratory setting, creating a larger army of cancer-fighting cells ready for reinfusion.
• Preparatory Chemotherapy: Patients receive a preparative chemotherapy regimen to prepare their body for the incoming immune cells.
• Cell Reinfusion and Growth: The expanded TIL cells are infused back into the patient, followed by a growth factor that helps these lymphocytes multiply further and seek out tumor cells throughout the body.

"As a care team, we witness firsthand the challenges faced by patients with advanced cancer who have exhausted all conventional treatment options," said Daniel Johnson, MD, medical oncologist and director of the Center for Innovative Cancer Therapies at Ochsner MD Anderson. "TIL therapy highlights how far cancer treatments have come. By utilizing a patient's own immune system in a highly personalized manner, we open new options for individuals with metastatic melanoma who have limited treatment choices".

Why Is TIL Therapy Such a Big Deal for Advanced Melanoma?

Advanced melanoma—classified as stage III or IV metastatic melanoma—is a form of skin cancer that has spread from its original location to other parts of the body, making it extremely difficult to treat. For decades, patients with this diagnosis had limited options once standard treatments failed.

The U.S. Food and Drug Administration (FDA) approved the first TIL therapy for advanced melanoma in 2024, following clinical trial results that demonstrated remarkable durability. Many patients continued responding to treatment five years after their initial infusion, with studies showing tumor shrinkage or complete elimination even when other treatment options had failed.

The concept of using immune cells found within tumors to fight cancer isn't entirely new—scientists discovered this potential in the late 1980s. However, it took decades of research and innovation to develop TIL therapy into a practical, FDA-approved treatment that could be safely administered to patients.

What About Safety Concerns With Immunotherapy?

While immunotherapies like checkpoint inhibitors have revolutionized cancer treatment since the first drug was approved in 2011, they can sometimes trigger serious side effects. Researchers at Cincinnati Children's Hospital have made an important discovery that could make these treatments safer.

About 2% of cancer patients receiving immune checkpoint inhibitors—drugs that work by blocking signals cancer cells use to hide from the immune system—develop myocarditis, an inflammation of heart muscle. Tragically, about half of these patients die from this complication, even if they survive their cancer.

Scientists discovered that this heart inflammation isn't caused by the treatment exhausting cancer-fighting cells. Instead, checkpoint inhibitors can trigger the creation of "autoreactive" T cells that mistakenly attack healthy heart tissue in addition to cancer cells. The research team identified a key driver: CD8 T cell-derived tumor necrosis factor (TNF).

In mouse models, blocking TNF signaling specifically through the TNFR2 gene product prevented this inflammatory cycle from starting in the heart. "Checkpoint inhibitors allow TNF signaling to trigger CD8 T-cells that are specific to antigens on cardiac myocytes, which in turn leads to life-threatening arrhythmias," explains Jeffery Molkentin, PhD, director of the Division of Molecular Cardiovascular Biology at Cincinnati Children's. "We used a targeted TNF blockade method to prevent this cycle in our mouse models. If these results can be replicated in humans, TNF blockade should prevent cardiac toxicity without compromising the anti-tumor benefits of checkpoint inhibitors".

While more research is needed to determine if a narrowly focused TNF inhibitor would be safe for human use and how long patients might need to take such a drug, these findings offer hope for preventing immune-related adverse events affecting the heart and potentially other organs.

What Other Advanced Immunotherapies Are Available?

Beyond TIL therapy, Ochsner MD Anderson also offers CAR-T cell therapy (chimeric antigen receptor T cell therapy), another form of advanced immunotherapy. While both approaches use a patient's own immune cells, they work differently. CAR-T therapy collects T cells from the blood rather than from the tumor itself, then genetically modifies these cells to target specific proteins found on cancer cells.

Ochsner MD Anderson was the first institution in Louisiana to offer CAR-T cell therapy to adults for treating certain blood cancers. The center continues to expand access to cutting-edge treatments, with research ongoing to study TIL therapy for other cancer types, including lung cancer.

For patients with advanced melanoma and other cancers, these personalized immunotherapies represent a fundamental shift in how medicine approaches cancer treatment—moving away from one-size-fits-all approaches toward therapies tailored to each patient's unique tumor biology and immune system.