Focusing on immune metabolism and tumor biology, this postdoctoral researcher works to overcome immunotherapy resistance.
Catherine Rono is a postdoctoral researcher in Scott Abram’s group at Roswell Park Comprehensive Cancer Center. Her work focuses on understanding how targeting metabolic pathways in immune cells can enhance antitumor immunity and improve responses to cancer immunotherapy. In this Postdoc Portrait, she shares the importance of her work and the research question she is most excited to answer next.
Targeting Metabolic Pathways to Improve Cancer Immunotherapy
Q | What scientific problem are you trying to solve?
Immunotherapies have transformed cancer treatment, yet their efficacy is often limited by the hostile tumor microenvironment, dominated by suppressive myeloid populations such as myeloid-derived suppressor cells and M2-like macrophages. My work addresses this challenge by targeting dihydroorotate dehydrogenase (DHODH), a key enzyme in de novo pyrimidine biosynthesis, to promote the differentiation of immature, immunosuppressive myeloid cells into functional antigen-presenting cells. By reshaping the tumor microenvironment, this approach aims to enhance durable antitumor immunity and broaden the fraction of patients who benefit from immunotherapy.
Q | What drew you to your research field?
My fascination with cancer immunology stems from both curiosity and a desire to make a tangible impact on patients’ lives. Early in my training, I became intrigued by how tumors can outsmart the immune system, actively reshaping their microenvironment to evade detection. This curiosity evolved into a deeper interest in uncovering the underlying rules that govern immune cell behavior, mechanisms that could be strategically leveraged to enhance the efficacy of current immunotherapies.
Unexpected Lessons and Misconceptions of Cancer Immunotherapy
Q | What’s one thing you learned from working on this research question that you didn’t expect?
One unexpected lesson from working on this project has been how metabolic stress induced by DHODH inhibition can serve as a powerful regulator of immune programming. Initially, I viewed nucleotide deprivation primarily as a strategy to starve cancer cells. However, I was pleased to find that rather than simply restricting growth, DHODH blockade actively reshapes myeloid cell fate in ways that enhance antitumor immunity.
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Q | What’s a common misconception about this area of research?
A common misconception is that cancer immunotherapy works solely by activating T cells. In reality, the success of T cell–mediated therapies depends heavily on the broader immune ecosystem, especially myeloid cells.
Towards Targeted Treatments and Clinical Strategies
Q | If your research succeeds, what could it change for science or society?
If successful, this work could redefine how we integrate metabolism-targeted therapies with immunotherapy. Rather than using metabolic inhibitors solely to attack tumor cells, we could deploy them strategically to reprogram the tumor microenvironment and sustain durable antitumor immune responses. Clinically, this approach has the potential to broaden the reach of immunotherapy, offering effective targeted treatment to patients who currently have limited treatment options.
Q | What question are you most excited to answer next?
I am most excited to define the precise molecular mechanism linking DHODH inhibition to the antitumor immune responses observed in vivo. Understanding this connection at a mechanistic level will not only strengthen the biological foundation of our findings, but it may also uncover predictive biomarkers that are essential for translating these insights into rational clinical strategies.
Responses have been edited for length and clarity.
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