University of Cincinnati Cancer Center presents research at AACR 2025

(Press-News.org) University of Cincinnati Cancer Center researchers will present abstracts at the American Association for Cancer Research Annual Meeting 2025 in Chicago.

Study finds contrasting effects of protein on head and neck cancer

A small protein called IL-9 has been shown to either contribute to or counteract tumor growth depending on the type of cancer, but its role in head and neck cancer has not been studied.

Abstract lead author Sam Nusbaum and her colleagues found IL-9 levels are increased in patients with head and neck cancer compared to healthy controls. 

“High mRNA levels of IL-9 in the tumor — or how much IL-9 is present in the tumor — are correlated with decreased survival in head and neck cancer patients,” said Nusbaum, a graduate student in the Cancer Center’s Head and Neck Experimental Advancement Laboratory (HEAL).

The team additionally found IL-9 increases the release of another protein from immune cells called IL-6, which has been found to decrease the ability of immune cells to target and kill tumor cells. 

However, IL-9 was not found to affect two types of immune cells that are critical in killing tumor cells. And in animal models, elevated IL-9 was associated with smaller tumor growth and smaller tumor weight.

“So far, I have seen both positive and negative effects of IL-9, so my future experiments will be focused on trying to figure out what is going on at a molecular level,” Nusbaum said. 

Nusbaum will present the poster “The role of IL-9 on NK and T cell infiltration and immune response to promote tumorigenesis in HNSCC” April 29, 2-5 p.m. Other coauthors of the abstract include Maria Lehn and senior authors Vinita Takiar, MD, PhD; Trisha Wise-Draper, MD, PhD; and Dalia El-Gamal, PhD.

Blocking signaling pathway found to reduce HNC tumor growth

Head and neck cancer (HNC) is the sixth most common cancer globally, and long-term survival rates with the most common type of head and neck cancer have remained stagnant for 30 years.

The human body is equipped with immune cells that can help attack cancer cells, and researchers, including first abstract author Lindsey Bachmann, focused on a specific type of immune cell called natural killer (NK) cells.

The team examined how a specific signaling pathway affects the ability of NK cells to attack HNC cells. Blocking the pathway was found to reduce tumor growth in animal models when NK cells and another type of immune cells, CD8+ T cells, are present.

“This suggests that this pathway and these immune cells play an important role in tumor growth,” said Bachmann, a medical student working in the Cancer Center’s HEAL facility.

Moving forward, researchers will focus on understanding the mechanisms that cause pathway blockage to lead to reduced tumor growth and how blocking the corresponding receptor in NK cells affects tumor growth in animal models.

“These studies are groundbreaking in the field of cancer immunology, and this research has the potential to lead to better treatments and more positive outcomes in patients with head and neck cancer,” Bachmann said.

Bachmann will present the poster “Investigating the role of CXCR2 in NK cells in head and neck cancer” April 29, 2-5 p.m. Other coauthors of the abstract include Donatien Kamdem Toukam, PhD; Lehn; Nusbaum; Katelyn Jansen; and senior authors Takiar, MD, PhD; Wise-Draper, MD, PhD; and El-Gamal, PhD.

Blood test a potential alternative for predicting tumor response to treatment

As treatments become more specific based on each patient’s unique cancer characteristics and mutations, it is imperative to predict patient responses to specific immunotherapy treatments and identify new biomarkers to advance personalized medicine.

Currently, the gold standard for diagnosing and assessing treatment response and tumor progression is tumor biopsy. But biopsies are not always a feasible, safe or sufficient option.

Researchers, including abstract first author Katelyn Jansen, are studying whether peripheral blood mononuclear cells (PBMCs) isolated from blood samples can be standardized and used as an alternative to tumor biopsies. Blood sampling is safe and more readily available to patients before, during and after treatment.

The team collected blood samples from eligible patients with head and neck cancer and processed the samples to isolate the PBMCs immediately or at eight and 24 hours after collection.

“The takeaway is that the time-delay for PBMC isolation from blood does not significantly impact the cell viability,” said Jansen, a co-op student working at HEAL.

Researchers also compared two different types of test tubes to collect the samples and found no significant difference, although one type of tube generally performed the best.

Moving forward, the team will need to validate their findings using patient samples shipped from other institutions and compare the PBMC findings to those from a traditional tumor biopsy.

“This research will be used one day hopefully to predict patient response to current immune checkpoint inhibitors and to identify new biomarkers to advance tailored therapeutics,” Jansen said.

Jansen will present the poster “Standardizing peripheral blood mononuclear cells processing for ex vivo evaluations to predict response to immunotherapy” April 28, 2-5 p.m. Other coauthors of the abstract include Farah Sagin; Claire Girten; Joanna Khoury; Tyler Hendrickson; Kelsey Dillehay McKillip, PhD; and senior authors El-Gamal and Wise-Draper.

Research examines combining immunotherapy with radiation for recurrent HNC

When head and neck cancers (HNC) recur after initial treatment, current standards of care include salvage surgery combined with X-ray-delivered radiation therapy (XRT). First author Jansen and her colleagues examined whether more targeted radiation through proton therapy (PT), used in combination with immunotherapy, could provide an even better response for patients.

“Both PT and XRT were effective in slowing tumor progression, and combination with immunotherapy led to modest additional benefits in tumor control,” Jansen said.

In animal models, either radiation therapy method was found to increase the amount of immune cells infiltrating tumors, but researchers only observed a minimal effect with the addition of immunotherapy.

“From here, the animal model will be modified to hopefully better see this more synergistic effect between the radiation therapy and the immunotherapy,” Jansen said.

Jansen will present the poster “Investigating the effects of radiation and anti-PD1 therapy on immune cell tumor infiltration in head and neck cancer” April 29 from 9 a.m. to 12 p.m. Other coauthors of the abstract include Lehn; Nicolas Nassar, PhD; Alexis Redmond; Mathieu Sertorio, PhD; and senior authors Takiar, El-Gamal and Wise-Draper.

Protein correlated with worse survival in breast cancer subset 

About 15% to 20% of breast cancers are HER2-positive, having elevated levels of the protein HER2, a member of the EGFR family. These cancers tend to grow and spread faster than breast cancers that are HER2-negative.

Researchers in the lab of Joan Garrett, PhD, studied how a protein called nonmuscle myosin IIA (NMIIA) influences progression, invasion and metastasis in HER2-positive tumors. First author Wasim Feroz said the team identified that NMIIA interacts with the protein HER3 and alters a signaling pathway linked to drug resistance and metastasis.

By testing tumor samples, the team found that although high NMIIA expression in lymphovascular invasion (LVI)-positive breast cancer correlates with worse survival, no survival difference was observed in LVI-negative patients.

The team is now exploring NMIIA expression in breast cancer metastases in the brain, the protein’s role in how cancer cells respond to physical forces and a new NMIIA inhibitor as a potential new treatment.

“Our findings suggest NMIIA as a key protein in breast cancer metastasis,” said Feroz, a graduate assistant in Garrett’s lab. “If our NMIIA inhibitor is effective, it could lead to new treatment strategies for HER2+ breast cancer.” 

Feroz will present the poster “Non-muscle myosin IIa role in breast cancer proliferation, invasion and metastasis” April 28, 2-5 p.m. Other coauthors include Sarah Storr, Andrew Stiles, Mary Kate Kilroy, Olamide Ogunleye and Garrett. 

Exploiting metabolic vulnerabilities in LAM 

Lymphangioleiomyomatosis (LAM) is a rare lung disease that primarily affects women and is characterized by a progressive and abnormal proliferation of smooth muscle-like cells in the lungs and other organs. Over time, LAM cells can destroy healthy lung tissue and result in respiratory failure.    

Researchers, including first author Evans Abor, studied how an enzyme called PHGDH influences the progression of LAM. They focused on how it affects the mTORC1 signaling pathway, a key driver of LAM, and explored whether blocking PHGDH could serve as a potential treatment strategy. 

“We found that PHGDH was highly expressed in LAM tissues, which suggested it might play an important role in disease progression,” said Abor, a PhD candidate in the UC Pathobiology and Molecular Medicine program who led this study in Jane Yu’s lab. 

Inhibiting the enzyme induced LAM cell death and significantly weakened the main signals (mTORC1) known to help LAM grow, including mitochondrial function and reducing the production of key complex substances the cells need to grow. 

“Specifically, we discovered that PHGDH supports LAM tumor growth while directly stabilizing the mTORC1 complex, which is crucial for cell maintenance and survival,” Abor said. “Combining PHGDH inhibition with rapamycin, an mTORC1 inhibitor, led to increased autophagy, a process where the cell recycles its damaged or unneeded parts.”   

Moving forward, the team plans to study how PHGDH inhibition affects LAM cells in preclinical LAM animal models, particularly in mice, and to continue exploring combination therapies that could help overcome current treatment limitations such as drug resistance and tumor regrowth,” Abor said. 

“This study opens up a promising new avenue for targeting metabolic vulnerabilities that support LAM tumor growth,” Abor said. “By focusing on PHGDH in LAM cells, we hope to develop therapies that will work alone or alongside existing inhibitors to provide more lasting control over the disease.” 

Abor will present the poster “Inhibition of PHGDH suppresses mTOR signaling and metabolic reprogramming in TSC2-deficient lymphangioleiomyomatosis cells” April 29, 2-5 p.m. Other abstract coauthors include Erik Zhang, PhD, and Yu, PhD.

Other Cancer Center research being presented at the conference:

Mary Kate Kilroy will present the poster “Co-targeting the HER family and mutant KRAS is efficacious in colorectal cancer” April 28, 2-5 p.m. Other coauthors include Cecilia Wischmeier, Briley SoYoung Park, Rosalin Mishra, Feroz and Garrett.

Tasnim Olatoke will present the poster “Stat1 promotes lesion growth and tumor immunity of tuberin-deficient cells in lymphangioleiomyomatosis” April 28, 9 a.m. to 12 p.m. Yu is an additional coauthor.

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