Growing up in Reykjavik, Iceland, Andri Lemarquis, M.D., Ph.D., remembers when his older brother Tomas developed an autoimmune disorder that destroyed his hair and fingernails. The episode propelled young Andri to search for a way to help. He didn’t need to look far.
“My grandfather had this big book collection, including books on science and medicine,” he recalled. “I learned all about the human body, and it was fascinating. I started telling all my friends, ‘I’m going to be a doctor and solve all the problems!’”
He was 8 years old.
A decade later, in medical school, Dr. Lemarquis was captivated by a professor’s lectures on T cells and the immune system. “I spoke to him,” he remembers, “went into his lab and started doing experiments.”
It all came together when Dr. Lemarquis treated his first patient, a child with acute lymphocytic leukemia. “I wanted to know more about how this disease works,” he said, “and I saw that the hospital was using the same tools as I was using in the lab.” He saw the importance of connecting research with treatment.
What also became clear was that he’d gone as far as he could in Iceland.
“That child needed a bone marrow transplant and had to go abroad to get it,” he said. “There simply wasn’t enough knowledge in Iceland.” He began what turned into a global quest, studying first in the Netherlands, then in Sweden and ultimately the U.S.
Before leaving Iceland, Lemarquis earned notoriety outside the medical field. In 2008, when he was 19, Dr. Lemarquis was one of nine protestors charged with forcing their way into the parliament building in Reykjavik.
This was during a time of political and financial upheaval in Iceland, including a banking collapse and accusations of governmental corruption. Tens of thousands of protestors would gather nearly every weekend.
The so-called “Reykjavik 9” claimed they were just trying to reach the visitors gallery — closed off by police — and express their views.
It’s hard to reconcile the image of the rabble-rouser with the soft-spoken, clean-cut, bespectacled man one now sees. These days, colleagues describe him as “humble,” “kind,” “collaborative,” “helpful,” “super creative” and, most often, “brilliant.”
At 35, Dr. Lemarquis heads the thymic regeneration division of the renowned laboratory of Marcel van den Brink, M.D., Ph.D., president of City of Hope Los Angeles and City of Hope National Medical Center and the Deana and Steve Campbell Chief Physician Executive Distinguished Chair. Dr. van den Brink originated the lab at New York’s Memorial Sloan Kettering Cancer Center, where he served for 24 years. The lab focuses on three areas aimed at improving cancer immunotherapy: the gut microbiome as an immune modulator, the mechanisms of chimeric antigen receptor (CAR) T cells in blood cancers, and the role of thymic regeneration in immune response and clinical outcomes.
Thymus and the Immune System
Devoting an entire division to the thymus — a small gland behind the breastbone — makes perfect sense given the major role it plays in the body’s immune system. T cells, those critical warriors that attack and destroy viruses, bacteria and other foreign invaders, including cancer, develop in the thymus. It is also where those cells learn to recognize a near-innumerable (“more than there are grains of sand,” says Dr. Lemarquis) number of threats to be neutralized.
“The thymus,” said Dr. Lemarquis, “is the school for our T cells.”
T cell production is robust in early childhood, but by puberty the thymus begins to diminish in a process called involution. Gradually, it produces fewer and less diverse T cells, leaving the body increasingly vulnerable to infections.
Cancer treatments, especially chemotherapy given before stem cell transplants, can injure the thymus and accelerate involution, a daunting outcome for young patients who see their disease arrested, only to face a lifetime without a healthy immune system.
Dr. Van den Brink’s lab looks for ways to “wake up” the slumbering thymus and restore its T cell production. It had been Dr. Lemarquis’ focus since authoring a paper showing how children who had received transplants seemed to be extra susceptible to the COVID-19 virus. “Our work is trying to boost the thymus in patients who might lose this basic protection,” he said.
Their collaboration began with a “cold call.”
While in Sweden, Dr. Lemarquis read about Dr. van den Brink. So he picked up the phone.
“He contacted me out of the blue,” said Dr. van den Brink. “I looked at his resume. It was intriguing. I was looking for people who were self-motivated, curious, people who would bring me new ideas. Andri had all that in spades. I trust my instincts. With Andri it was immediately clear.”
When Dr. van den Brink joined City of Hope, he asked Dr. Lemarquis to lead the lab’s transition to California and grow the thymic regeneration department. Dr. Lemarquis didn’t have to think twice (“I told Marcel I’d follow him to hell and back,” he says). The family packed up and drove across the country — a safer option than flying for Dr. Lemarquis’ wife, eight months pregnant with their third child.
Once here, Dr. Lemarquis quickly set about fulfilling his mission, expanding thymic research into a full-fledged lab-within-a-lab — it’s now the largest of the three branches — and making plenty of friends and fans along the way.
“We both recognize that cancer and its treatments cause physical and biological problems that are irreversible,” said Saro Armenian, D.O., M.P.H., director and professor in the Division of Outcomes Research/Intervention, Department of Population Sciences, and the Barron Hilton Chair in Pediatrics. Dr. Armenian is providing transplant patient data to Dr. Lemarquis in order to track changes in immune response over time and identify the treatments that drive that change. He enjoys the working relationship. “He is one of our most brilliant, young new scientists,” said Dr. Armenian.
Colleagues in Dr. Lemarquis’ lab relish being mentored by him.
“He’s this powerhouse of science,” said postdoctoral fellow Madeline Lauener, Ph.D., whose own interest in the field developed after battling lymphoma as a teen. “He’s always looking ahead at the whole picture. But he’s very humble, always there to answer my questions.”
“He’s very kind,” added research associate Miriam Martinez, who is grabbing the opportunity for hands-on experience before heading to medical school. “He’s passionate. His mind runs 100 miles an hour with experiments.” (She’s careful not to approach him when he’s engrossed in the data on his computer screen. “He’ll jump! He startles easily,” she laughs.)
Dr. Lemarquis pleads guilty. “I fall asleep and wake up with my science,” he says. “I love data and moving things forward. I get excited about human processes and the basic mechanisms of immunology.
“Maybe I have too many ideas.”
One of those ideas may be a game-changer. Dr. Lemarquis has discovered something important about regulatory T cells, or “Tregs.”
Focusing on T Cell Production
When normal T cells target an invader, Tregs make sure the attack doesn’t go too far, stopping the assault before healthy tissues are attacked as well. Dr. Lemarquis has uncovered a novel and previously undescribed population of Tregs that accumulate in the thymus after injury and secrete a growth factor called amphiregulin. In preclinical research, Dr. Lemarquis and his collaborators have shown that when these Tregs are added to the bloodstream intravenously, they find their way back to the thymus, where amphiregulin then helps teach the thymus to regenerate and develop more T cells.
It could be the path toward one day maintaining a working thymus, and its T cell production, for a lifetime.
Dr. Lemarquis recently published these findings, a collaboration with an international team of scientists, in the journal Immunity. Dr. van den Brink was the senior author.
“Our discovery hasn't been described before and represents a novel pathway to regeneration in the gland,” said Dr. Lemarquis. “The findings open up a new translational angle for addressing thymic fatigue and damage.
“We have a thymic research program now at City of Hope, with computational biologists and postdoctoral scholars who are working on different projects, along with collaborators in the clinic who can help move our findings forward,” said Dr. Lemarquis. “I think there is great potential for Tregs and amphiregulin to be used therapeutically in patients receiving cancer therapies to ameliorate immune function.”
Drs. Lemarquis and Van den Brink have become friends, sharing their interests in art, music and theater. “He’s also a very good cook,” adds Dr. van den Brink, though he draws the line at Dr. Lemarquis’ passion for traditional Icelandic foods, such as fermented shark.
Dr. van den Brink believes his young protege is onto something with regulatory T cells, as well as other areas. He’s eager to see where it all leads.
“I love what he’s doing,” said Dr. van den Brink. “He’s still young, but he has all the potential to become one of our leading scientists.
“I’m counting on that.”