Enlisting an unlikely ally to fight cancer

“My dream is to make a lasting impact on how we think about cancer treatment.”

Meet MacLane Watson

The tumor microenvironment is incredibly hostile to the body’s immune system, posing serious problems for the glucose-dependent effector cells that rush to the body’s defense: once they arrive they’re forced to compete with the tumor for scarce resources. However, this bleak microenvironment isn’t inhospitable to all. In fact, the tumor exploits a subset of immunosuppressive T cells called regulatory T (Treg) cells to support its own growth and survival. This exploitation got University of Pittsburgh immunology researcher McLane “Mac” Watson wondering, “What makes Treg cells able to thrive under these metabolically harsh conditions?”

“Unlike immune effector cells that depend on glucose, Treg cells seem to use an alternative fuel source like lactic acid as energy,” Watson explains. “Treg cells don’t compete. Instead, they’re able to use metabolites produced by tumor cells to function. Think of Treg cells as flex fuel vehicles, able to utilize alternative fuels when normal fuel is limiting.”

Watson’s study of how to leverage Treg cells’ metabolic flexibility to boost the body’s antitumor response stands out—so much that his research earned him a spot on the 2017 Society for Immunotherapy of Cancer (SITC) conference’s roster of speakers. That’s quite an achievement for any scientist, let alone a second-year PhD student. Relying on his training as a concert cellist to help remain calm and composed, Mac delivered the conference’s lone presentation focused on Treg cells. Afterward, he fielded pointed questions from experts about his work and how it plays into the larger field of immuno-oncology. “They were quite curious about the greater implication of metabolites from the tumor cells and how they regulated Treg cells,” Mac recalls.

“Failure helps me learn by pushing me to adjust my approach and dig deeper into the details.”

That curiosity is well-founded. “Treg cells have the metabolic flexibility to utilize strange metabolites,” Watson explains. “For example, the idea that Treg cells can rely on lactic acid—rather than oxygen and glucose—to survive in the tumor environment is very novel. If we can manipulate and target Treg cell metabolism, we can improve immunotherapies and slow tumor growth.”

Watson has begun to form his own identity in the large immuno-oncology research field by taking ownership of a key area of investigation in the laboratory of Greg Delgoffe, PhD, recipient of a 2017 NIH Director’s New Innovator Award for his study of immunotherapy in the tumor microenvironment.

As a concert cellist, Watson knows the power of team collaboration to pool talents and strengths, improve skills, and create something beautiful. Just as musicians in an orchestra work together to discover deeper details and create meaningful work, Watson encourages other scientists to try new collaborative approaches.

“Social platforms are part of our development process and unique to my generation.”

Watson uses social media to engage his peers and exchange information in ways he hopes will help speed everyone’s research and generate more discoveries.

“Our lab uses Twitter and other social media to increase our presence and awareness of our lab’s accomplishments,” Watson says. “I share links to our publications, notifications of our funding, and interesting and funny things that happen daily in the lab. This communicates our name to the scientific community and could help to attract great students, postdocs, and fellows to our lab. Social sharing is now part of a researcher’s development process and unique to my generation.”

Despite his early successes Watson is no stranger to setbacks and the need to push forward in spite of them. “Science is often a lot of not getting it right,” he muses. “Failure helps me learn by pushing me to adjust my approach and dig deeper into the details.”

Certain tools are essential to the daily work and longer-term goals in the Delgoffe lab. Watson uses Invitrogen MitoTracker and CellTrace viability/proliferation dyes, for example, because they help him measure mitochondrial mass and identify the specific effects that metabolite manipulation has on immune cells in the tumor microenvironment.

Armed with those tools and a willingness to collaborate with and learn from his peers, Watson is already pushing the boundaries of immuno-oncology on his quest to deliver new, life-saving cancer treatments.

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