A recent study of a type of immune blood cells associated with resistance to certain treatments for melanoma is one sign of the growing role of data science in solving some of medicine’s most puzzling riddles, says Hatim Sabaawy, MD, PhD, associate director of translational research at the University of Colorado Cancer Center.
The development of the anti-cancer immunotherapy drugs called immune checkpoint inhibitors has improved treatment for many cancer patients, but patients with mucosal melanomas — melanomas that occur not on the skin but in the mucous membranes in the head, neck, eyes, respiratory tract, and genitourinary region — are particularly resistant to immune checkpoint inhibitors for reasons researchers don’t fully understand.
For years, surgery for patients with stage III melanoma — melanoma that has spread to the lymph nodes — involved removing those lymph nodes along with the primary tumor. Known as completion lymph node dissection (CLND), the surgery was meant to ensure that no cancer remained after surgery.
The Tumor-Host Interactions Program (THI) at the University of Colorado Cancer Center has awarded four CU Cancer Center researchers $30,000 each to gain preliminary data using the Multiplex Ion Beam Imager (MIBI) housed in the cancer center’s Human Immune Monitoring Shared Resource (HIMSR) to support a competitive national grant proposal. The selected researchers are expected to submit a national competitive grant proposal within six months of completing their THI-MIBI pilot studies.
Recent advances in immunotherapy have allowed doctors at the University of Colorado Cancer Center to more effectively treat melanomas that spread to other parts of the body. Immunotherapy drugs such as checkpoint inhibitors, which are commonly used to treat melanomas, work to strengthen a patient’s immune system so that it can prevent a tumor from “turning off” the ability of the immune system to fight it.
Though people most often think of melanoma as affecting the skin, the cancer can occur anywhere in the body where pigment-producing melanocyte cells are found. That includes mucous membranes in the head, neck, eyes, respiratory tract, and genitourinary region.
“For Christmas, we took a family photo with all the grandkids,” says Sam’s wife, Janet. She went on to explain, “The kids wanted to take this photo because they thought Sam would not be here next Christmas.”
We all know that in the spring or before going on a beach vacation, it’s important to get a solid tan so that we don’t get burned. After all, it’s sun burns and not sun tans that cause skin cancer, right? Not so fast, says Neil Box, PhD, University of Colorado Cancer Center investigator and president of the Colorado Melanoma Foundation.
During COVID19, getting outside for socially distanced activities is one of the few forms of available recreation. But more people getting out also means more sun exposure, and so during Skin Cancer Awareness Month, University of Colorado Cancer Center reached out to one of our members, Neil Box, PhD, president of the Colorado Melanoma Foundation, to learn about the risks and how to stay safe.
In melanoma, myeloid-derived suppressor cells (MDSCs) are bad – the more MDSCs, the poorer a patient’s prognosis. That’s because when these MDSCs expand to accumulate near melanoma tissue and in blood circulation, they suppress the immune system so that it doesn’t attack the cancer. But how do MDSCs expand and how do they accumulate near melanoma tissue?
When you think of melanoma, you picture the sun. But there is another class of these dangerous cancers that has nothing to do with sun exposure. Mucosal melanomas arise seemingly spontaneously from mucosal tissues, accounting for about 1.3 percent of all melanomas. In part because most of these tissues are hidden, mucosal melanomas tend to be diagnosed late. Late diagnosis combined with lack of response to many newer treatments (especially immunotherapies), leads to a 5-year survival rate for rare melanomas less than half that of the more common form of the disease.
There are marathons and then there’s the Boston Marathon, when the city takes a holiday and 500,000 people line the streets ten-deep to cheer on runners from all over the world. This year, Jeremy Hugh, who was born just north of Boston in Nashua, NH, will be running with them.
“My birthday is within a few days of the marathon and my dad and I always used to go down to watch. I’ve been to I don’t even know how many Boston Marathons, since about age five, all through college at U. Mass, until heading off for med school in New York,” says Hugh, who is a University of Colorado Cancer Center investigator and skin cancer specialist at Rocky Mountain Regional VA Medical Center.
There are two ways to earn an invite to run the Boston Marathon. First, you can be astoundingly fast, running a qualifying time of about three hours for Hugh’s age group; or second, you can fundraise for one of the marathon’s charities. Hugh chose the second option, and maybe it’s not a surprise that he chose to fundraise for IMPACT Melanoma, an organization that raises awareness about the need for sun protection to reduce the risk of skin cancer.
“I’ve been wanting to do it and figured now is a good time. We’re probably going to start a family soon and so now seems like the best time to train. I started looking into it the last couple years and decided to apply this year,” Hugh says.
According to Hugh, melanoma is one of the cancers for which awareness makes a big difference.
“If you get it early enough, it’s not that big of a deal, but if not, there’s a pretty good chance of dying from it. What that means is that awareness is a big deal – it’s something where awareness can have a big impact,” says Hugh, who recently volunteered with the Sun Bus to offer free skin cancer screenings at the Denver Veteran’s Day parade.
Not only does Hugh spend his own time offering free skin cancer screenings and fundraising for IMPACT Melanoma, but he recently wrote a scientific paper using the organization’s data on how the placement of free sunscreen dispensers affects awareness of skin cancer risk and sun-safe behaviors.
“The other thing they do is educate people who do hair or work in nail salons, massage therapists, etc., so if they see something suspicious, they can send people to a dermatologist. Plenty of times in my short career that’s the reason someone with melanoma comes to us,” Hugh says.
If you’re thinking about helping Dr. Hugh raise money for the race, here’s a little something to sweeten the deal: a $25 donation to his team earns entry into a raffle supported by Dr. Hugh’s dermatologist friends (specify if you’d like to be in any of the drawings when you donate!). Prizes include an area of Botox ($300 value), a $300 credit at the cosmetics center, or a vial of Jovederm filler treatment at the CU Boulder Dermatology office ($575 value).
“This was my city growing up, and the marathon is an iconic thing that Boston has,” Hugh says. “I feel lucky to be able to combine this event that has always meant so much to me with my current work in skin cancer. If feels like a real milestone.”
Melanomas tend to be “hot” or “cold” – if they’rehot,immunotherapy lights melanoma tumors like beacons for elimination by the immune system; but 40-50 percent of melanomas arecold,making them invisible to the immune system, and patients with cold tumors tend to show little benefit from immunotherapies. The problem is that it’s been impossible to distinguish a hot melanoma from a cold one – the solution has been to administer immunotherapy and hope for the best, often leading to wasted time and resources. Now a University of Colorado Cancer Center study presented at the American Association for Cancer Research (AACR) Annual Meeting 2019 identifies a possible way to predict which melanomas are hot and cold: Tumors with mutations in genes leading to over-activation of the NF-kB signaling pathway were more than three times as likely to respond to anti-PD1 immunotherapy compared with tumors in which these changes were absent.
It seems like everybody’s got a story about that “one bad burn” – the time you fell asleep next to the pool and tattooed a white handprint on your lobster-red chest, or forgot to pack the sunscreen while hiking a Colorado 14er. As you know, sunburn increases your chance of developing melanoma and other skin cancers. But what about just one bad burn? And what can you do about it now?
CU Cancer Center member Christopher Lieu, MD, and Namrata Vijayvergia, MD, of the Fox Chase Cancer Center conclude their discussion with considerations for managing immunotherapy-related toxicities in patients with metastatic hepatocellular carcinoma (HCC), along with a review of the available evidence regarding the duration of immunotherapy treatment.