How 2 CRI Scientists Fight Cancer by Mimicking Infection and Characterizing Molecular Mechanisms in Immune Cells

Immunotherapy harnesses the power of the immune system to target cancer with precision. Approved by the FDA for 29 types of cancer, this breakthrough approach is rapidly advancing thanks to the Cancer Research Institute (CRI) and CRI-funded scientists. CRI not only accelerates cancer research but also champions scientific diversity through initiatives like the CRI Irvington Postdoctoral Fellowship to Promote Racial Diversity, supporting underrepresented communities. We also expand access with our annual Spanish-language immunotherapy summit and a fully accessible Spanish website. 

During National Hispanic Heritage Month, CRI is proud to highlight the perspectives and achievements of Hispanic scientists’ potentially life-saving work that can accelerate progress for countless cancer patients. CRI-funded scientists’ areas of research vary—Alejandro Villagra, PhD, associate professor of oncology at Georgetown University and CRI CLIP Investigator, conducts research on melanoma to categorize the molecular mechanisms involved in controlling the phenotype and function of immune cells. Megan Molina, PhD, senior fellow in the Oberst Lab at the University of Washington and CRI-Bristol Myers Squibb Postdoctoral Fellow, seeks to pierce solid tumors by imitating infection. Dr. Molina is supported by the CRI Irvington Postdoctoral Fellowship to Promote Racial Diversity.

“The most powerful tool to raise awareness in a specific population is involving members of these groups in the issue and allowing them to be part of the solution,” Dr. Villagra told CRI during a discussion about National Hispanic Heritage Month. Both Drs. Villagra and Molina were gracious enough to talk about cancer treatment and care disparities in the Hispanic community while also providing rich insight about their specific immunotherapy research.

The goal of my work is to engineer immune cells that can replicate that response to infection and effectively tip the scales enough that immune cells can properly mount an anti-tumor response.”

Megan Molina, PhD, CRI-Bristol Myers Squibb Postdoctoral Fellow

Hope for Progress

Immunotherapy unites diverse research efforts toward the goal of defeating cancer. Dr. Molina focuses on disarming solid tumors, while Dr. Villagra explores immune cell responses to melanoma—both aiming to improve patient outcomes against deadly cancers. 

“There are many exciting, new strategies for targeting various aspects of tumor immunology for cancer therapy,” Dr. Molina said. “I think a multi-pronged approach will be most advantageous for improving patient outcomes. That means, in the near-term, studies on how to safely combine multiple therapies will drive the next generation of cancer immunotherapy.” CRI-funded scientists have demonstrated recent progress against solid tumors, specifically in illuminating the interaction between immune system and cancer cells. 

One of the major challenges in targeting melanoma with immunotherapy is the proper and timely identification of resistance.”

Alejandro Villagra, CRI CLIP Investigator

“We know that some important mechanisms of resistance to immunotherapy in melanoma are due to the strong immunosuppressive tumor microenvironment (TME),” Dr. Villagra explained. He said several new approaches that aim to reduce the anti-inflammatory and immunosuppressive setting in tumors have shown promising results when combined with immunotherapies like checkpoint blockades, which take the ‘brakes’ off the immune system, unleashing its full potential against cancer. 

Characterizing Molecular Mechanisms in Immune Cells to Improve Melanoma Patients’ Outcomes 

Melanoma is a cancer of extremes—rare in diagnoses but leading in skin cancer deaths, with over 100,000 cases and 8,000 deaths expected in the U.S. in 2024. Yet, immunotherapy has significantly improved outcomes, especially when caught early. Similarly, breast cancer mortality has dropped from over 33% per 100,000 in 1990 to under 19% in 2022, thanks to advances in treatment. 

Dr. Villagra’s research centers on how certain processes affect the traits and behavior of immune cells within the context of melanoma. He said his focus is on epigenetic and metabolic modulators, compounds that can alter how genes are expressed and how cells use energy, that occur in macrophages—a white blood cell that destroys microorganisms, removes dead cells, and supercharges cancer-combating activity in immune system cells. Dr. Villagra stated he wants to identify and engineer novel therapies to control characteristics that support and thwart tumors. 

“My initial background was in epigenetics. When doing my postdoc, I realized very little was known about epigenetic control of immune function,” he explained. Dr. Villagra uses his epigenetics expertise to address this knowledge gap in the immunotherapy space.  

In September 2024, he was the senior author of a research paper that analyzed the balance between antitumor and tumor-promoting macrophages in melanoma, and how to tip the scales in favor of the former. The study determined that reprogrammed macrophages as a form of adoptive cell therapy, a type of immunotherapy that channels immune cells to attack cancer, resulted in hindered tumor growth in mouse models. 

Can Immunotherapy Pierce Through the Protective TME of Treatment-Resistant Solid Tumors? 

Solid tumors pose a tough challenge for immunotherapy due to immune cell exhaustion in the TME. Dr. Molina’s innovative approach aims to outsmart cancer cells, allowing immunotherapy to break through and deliver more effective treatment. 

“Cancer cells perpetuate a highly hostile and immunosuppressive environment within the walls of a tumor. Immune cells that enter the tumor become overwhelmed,” she told CRI. “While groundbreaking therapies like immune checkpoint blockades can essentially ‘take the brakes off’ the immune system, many of the T cells present are still unable to ‘press the gas pedal.” 

Part of the larger challenge Dr. Molina tackles in her research is that the immune system must be coaxed to attack solid tumor because it cannot always differentiate a biological threat from its own normal cells. “Something that isn’t necessarily obvious is that when cancer cells are proliferating out of control, your immune system must act against its own nature and choose to kill cells that it recognizes as ‘self,’” Dr. Molina explained. Her research goal is to create and deploy tumor-targeting T cells that can then be activated within the TME. This strategy is designed to maximize precision and power while limiting unintended side effects.  

Thanks to the dedication and focused research of scientists like Drs. Molina and Villagra, we are closer to creating a world immune to cancer.