Then and Now: Yvonne Saenger’s Passion for Translational Research

Physician scientist and immuno-oncologist Yvonne Saenger was working on understanding the complex tumor microenvironment, identifying biomarkers of immune response, and developing combination immunotherapies at Columbia University when The Scientist first profiled her in 2015. She was determined to do research that would have a positive impact on the lives of patients with cancer. “It’s challenging because you have to be comfortable in both worlds,” Saenger said at the time.

Currently at the Albert Einstein College of Medicine, Saenger has continued to make discoveries in immuno-oncology and immunotherapy, pursuing targets in melanoma, liver cancer, and more. For The Scientist’s 40^th anniversary, Saenger discussed how her career has progressed, her recent projects, and the importance of team science. What has powered her accomplishments over the last 11 years is the same drive to make an impact in the clinic. “My passion is really translational research,” she remarked.

Identifying Biomarkers for Melanoma Recurrence

Melanoma has been one of Saenger’s main focus areas, particularly the identification of biomarkers for melanoma recurrence.¹ To do so, Saenger and her team have explored a variety of approaches, including the use of immune-related gene signatures. “It's really [about] looking at the tissue to detect whether the immune system is strong enough to keep the melanoma from coming back,” said Saenger. They validated the approach using clinical samples from a massive long-term study of melanomas, Saenger said—one of the accomplishments she is most proud of. “It was great to access those samples and be able to test our hypothesis,” she said. “That was very exciting.”

In collaboration with medical oncologist David Rimm of Yale University, the team has also stained different immune subsets within tumor samples and implemented machine learning to analyze them.² “We've been looking at digital analysis of images, looking at quantifying tumor-infiltrating lymphocytes [in the tissue],” she explained. The goal, as always, is to improve clinical outcomes in patients. “If they're at higher risk [of recurrence], then you might prioritize them for more monitoring and possibly more intense adjuvant therapy to prevent the recurrence,” Saenger added.

Another of Saenger’s projects focuses on a specific subset of melanomas that occurs on the palms of the hands, in the nail bed, and on the soles of the feet. “That's the kind of melanoma that people of all pigmentation levels get,” she said. “We have a lot of Hispanics and African Americans in the Bronx, and they do tend to get those types of melanomas, so we've been looking at the immune infiltrates in them and evaluating them.” Saenger’s team has uncovered key differences in the genetics and immune parameters of these melanomas: “They definitely have a different immune microenvironment [that’s] a bit less favorable than the other melanomas.”

Liver Cancer, Oncolytic Viruses, and the Importance of a Multidisciplinary Approach

Outside of her significant efforts in melanoma, Saenger has researched many other solid tumors, including pancreatic and prostate cancers. One of her current projects focuses on hepatocellular carcinoma (HCC) and specifically, exploring the role of the complement system. Complement proteins, produced by the liver, are ubiquitous throughout the body and have a range of different functions in immunity.

“We've found that even though patients with liver cancer have lower levels of complement in the blood—probably because they're just sicker and the liver is making less complement—the complement proteins accumulate at high levels within the tumors,” Saenger explained. It appears that the interaction between the complement proteins and particular receptors drives tumor progression in HCC.³ “[But] we don't fully understand all the impacts on the immune system, which are very diverse,” she said.

Saenger continues to use her research insights to develop better treatments for cancer, including combination immunotherapies and oncolytic virus therapy. “I'm still very interested in the oncolytic viruses and [I’ve been] doing some work in mice with these,” she said.

Looking back at her original profile, Saenger said that it was very encouraging at a time when she was so focused in the lab. “The overall ultimate aspiration is to make [the research] impactful, so that it actually affects patients, which is a very lofty goal that we all have,” she said. “So, it's nice to get encouraged that people actually care about this type of work, especially [when] I think nowadays, there's a lot of stress in science in the U.S.”

The key mindset shift for Saenger recently has been in realizing she doesn’t need to do everything herself. “What I've learned most over the past 10 years is just how important team science is, and how important it is working with a group of collaborators to get multiple inputs and viewpoints, and actually access more resources and ideas,” she said. As for the future, Saenger will continue combining computational methods with immunology to continue to drive positive impacts, something she will focus on in her imminent new role at Stony Brook University. “In 10 years’ time, I really want to have built up more of an ecosystem at my new job where we really integrate basic research with clinical science,” said Saenger.