This story is part of a series, Out of Balance, profiling a few out of the millions of people around the world living with immune-related diseases. Their journeys are what inspire researchers at the Allen Institute for Immunology in their quest to unlock the mysteries of the immune system and ultimately to improve patients’ health and well-being.

Maria Melvin can credit a dress for catching her cancer early.

If she hadn’t worn that particular dress — which dips low in the back — to an event at the hospital where her mother worked, and if her stepfather, who was also at the party, hadn’t been familiar with the signs of skin cancer from his own earlier bouts with the disease, the cancerous moles between her shoulder blades might have gone unnoticed for much longer.

And that could have been disastrous. Unlike her stepfather, who had the more common and rarely dangerous type of skin cancer known as squamous cell carcinoma, Melvin had melanoma, a rare but often highly deadly form of skin cancer.

Melvin, who is from Port Angeles, Washington, was 22 at the time and just finishing college. She was about to start nursing school. The idea that she could have cancer was the farthest thing from her mind. She was vaguely familiar with melanoma but had no idea it could kill you.

“I assumed since it was skin cancer that it was something easily treated, not that it was potentially fatal like other types of cancer. I thought it was no big deal,” she said.

But after she’d had the moles biopsied and her primary doctor referred her to a skin cancer specialist, who sent her for a chest x-ray and more rounds of lab work, Melvin realized this wasn’t just a quick-office-visit mole. She started doing some reading, and some surprising statistics jumped out at her: Although melanoma is relatively rare, accounting for just one percent of all skin cancer cases, it causes the vast majority of skin cancer related deaths.

“That was humbling and scary,” Melvin said.

She had two moles removed — the surgeon had to take 6-centimeter-wide pieces out of her back to get the edges — and some lymph nodes. The doctors found that, luckily, the cancer hadn’t spread beyond those two spots, meaning Melvin wouldn’t need any treatment other than surgery and ongoing monitoring. In the ten years since her diagnosis, she’s had regular skin checks, five more melanomas removed since the original two, and countless other biopsies.

But she feels very lucky to have found the cancer early enough that extra doctor visits and minor surgeries are all she has to put up with. Metastatic melanoma, or melanoma that’s spread to parts of the body beyond the original tumor, is a very different story.

Studying late-stage melanoma

Most patients treated for early-stage melanoma survive their disease. Those with advanced disease, where the cancer has spread throughout the body, only have a 23 percent chance of surviving five years past their diagnosis.

In the past decade, treatments new to the market may be chipping away at that statistic. For reasons researchers don’t fully understand, melanoma is especially sensitive to attack by immune cells, meaning that immunotherapies, treatments that enhance or alter patients’ own immune systems, are showing particularly promise for this type of cancer.

One of last year’s Nobel Prizes was given to researchers who helped pioneer a type of cancer immunotherapy called a checkpoint inhibitor, a drug that releases the “brakes” on patients’ existing immune cells, allowing them to more effectively find and kill cancer cells. Checkpoint inhibitors seem to work especially well on metastatic melanoma, but “success” for a metastatic cancer is a somewhat low bar — the drugs only work for around 20 percent of patients, and it’s not clear why they help some people but not others.

“This cancer is not solved despite a Nobel Prize,” said Tom Bumol, Ph.D., Executive Director of the Allen Institute for Immunology, a division of the Allen Institute. “The best predictor of long-term survival is still early detection and surgery.”

Together with a team of researchers at the University of Pennsylvania led by John Wherry, Ph.D., Bumol and his Allen Institute colleagues are hoping to find answers to why checkpoint inhibitors don’t work for all melanoma patients. They’re planning to carefully follow the changes in immune cells in the blood of patients with metastatic melanoma who have received the treatments and to capture any differences that might go hand-in-hand with better or worse outcomes, with a particular focus on enhancing immune capabilities to help patients.

Survivorship informs work

As with other skin cancers, fair skin and unprotected sun exposure or tanning bed use are risk factors for melanoma. Melvin isn’t sure why she drew the short straw — she is fair-skinned but doesn’t remember getting a lot of sunburns as a child, and said she used tanning beds occasionally as a teenager.

She started nursing school shortly after her diagnosis, but the cancer wasn’t the primary motivator for that decision, she said. Her father had died of a heart attack a few years earlier and that spurred her to go into the medical field. Melvin, who’s now 32 and living in Port Angeles with her husband and two sons, works as a hospital nurse and sees surgery patients before and after their care. She’s also finishing a master’s program to become a family nurse practitioner. Her experience as a patient herself has made her a better nurse, she said.

“It’s a good reminder that when you’re on the other side of that gown, you’re terrified and you’re uncomfortable,” Melvin said. “It’s easy for medical providers to assume that patients know what’s going on because we do it every day and these things are no big deal to us, but it’s a huge deal to patients.”

Bumol, who is also a recent melanoma survivor, has a long history with the disease even before his diagnosis. Decades earlier in his research career, he was part of a research team studying melanoma, back when there were very few treatment options for patients with advanced forms of the disease. Coming full circle to study it again, in the era of immunotherapy, is satisfying, he said.

“In the 80s and 90s, we were all hoping for something that would help, because there were few options. So immunotherapy is a great platform for hope and new discoveries,” Bumol said. “But there’s much more to be done.”