Moffitt Studies Advance Cancer Research Through Diet Analysis, Spatial Biomarkers, and Engineering

Moffitt Cancer Center researchers have published multiple studies advancing understanding of cancer risk factors and treatment prediction while hosting a national summit on engineering innovations in cancer research.

A new study published in the British Journal of Cancer suggests that people who follow plant-based diets may have a slightly lower overall risk of developing cancer compared with people who regularly eat meat. Researchers combined data from several large prospective cohort studies that tracked cancer diagnoses among people who reported different dietary patterns, including meat-eaters, vegetarians and vegans. Overall, the study found that vegetarian diets were associated with a noticeable reduction in overall cancer risk compared with diets that included meat.

The study also identified some unexpected associations for specific cancer types. Vegetarians had a higher reported risk of esophageal squamous cell carcinoma, while vegans showed a higher risk of colorectal cancer. The researchers emphasize that these findings require further investigation and should be interpreted cautiously.

A researcher at Moffitt Cancer Center who studies nutrition and cancer risk says plant-based diets contain several features that could help explain the overall cancer-protective trend. Plant-based diets tend to be rich in fiber, antioxidants, vitamins, minerals and phytochemicals that help reduce inflammation, support healthy gut function and protect cells from DNA damage. They also tend to be lower in saturated fat and more nutrient dense, which can help maintain a healthier body weight, an important factor in cancer prevention.

The study is observational, meaning it can identify associations but cannot prove causation. Even with a very large sample size and long follow-up, people who choose vegetarian or vegan diets may differ from meat-eaters in other health-related behaviors such as smoking, alcohol use, physical activity or screening habits. The findings support the idea that plant-based diets may reduce cancer risk, but they do not prove that switching diets will directly cause risk to fall.

One hypothesis for the esophageal cancer finding is that some vegetarians may consume lower levels of specific micronutrients such as zinc or selenium that play roles in maintaining the integrity of the esophageal lining. Another possibility is that lifestyle or cultural factors not fully captured in the data differ between vegetarians and non-vegetarians in certain regions. The higher colorectal cancer risk reported among vegans may also reflect differences in nutrient intake or other lifestyle factors. Vegan diets can vary widely across and within populations and some may be low in calcium, vitamin D or B12, which are nutrients associated with colorectal cancer protection.

In separate research published in Cancer Research, Moffitt researchers identified distinct spatial tumor–immune ecosystems that predict whether patients with advanced non–small cell lung cancer will benefit from immunotherapy. The findings show that analyzing how tumor and immune cells are organized and interact within the tumor microenvironment may predict disease progression more accurately than PD-L1 status alone. The paper was featured on the cover of the publication and is also part of its Data Science special series.

Using multiplex imaging, spatial statistics and machine learning, investigators analyzed paired pre- and on-treatment biopsies from patients enrolled in a clinical trial combining the HDAC inhibitor vorinostat with the PD-1 inhibitor pembrolizumab. Rather than focusing on single markers, the team examined how immune cells and tumor cells were positioned relative to one another, defining spatial "neighborhoods" and broader tumor–immune ecologies.

Tumors from patients whose disease progressed were characterized by an immune-suppressive architecture before treatment began, including greater spatial clustering of FoxP3-positive regulatory T cells and PD-1–expressing immune cells near tumor cells. In contrast, tumors from patients with stable disease showed stronger colocalization of CD3- and CD8-positive effector T cells interacting with tumor cells. These findings suggest that response to immunotherapy may be influenced by preexisting spatial organization within the tumor microenvironment.

When researchers trained predictive models using these spatial ecosystem features, they achieved up to 87.5% accuracy in forecasting disease progression. By comparison, using PD-L1 expression alone resulted in approximately 63% predictive accuracy. The results support expanding lung cancer diagnostics beyond single-marker testing toward spatial biomarkers that may help guide more precise immunotherapy decisions.

The primary goal was to define and quantify distinct tumor–immune ecologies in non–small cell lung cancer and determine whether these spatial patterns can predict disease progression and response to immunotherapy. Treatment response depends on how cells are spatially organized and functionally interacting, not just whether specific markers are present. Responders had tumors that were more immune-permissive before treatment. Non-responders had tumors with a suppressive spatial architecture that limited effective immune attack. These ecosystem patterns were largely present before therapy began.

The findings support moving beyond single-marker testing toward ecosystem-based patient stratification. Patients with immune-permissive ecosystems may benefit from checkpoint inhibitors alone, while those with suppressive ecosystems could be directed toward combination therapies or clinical trials earlier. While not yet routine, multiplex immunohistochemistry and digital pathology platforms are becoming more common. With further validation and streamlined computational tools, spatial immune profiling could become part of lung cancer diagnostics in the coming years.

This study was supported by the National Cancer Institute (U01CA232382, U54CA274507), the Moffitt Center of Excellence for Evolutionary Therapy and the Moffitt Lung Cancer Center of Excellence.

Researchers, engineers, clinicians and policy leaders gathered in Tampa for the fourth annual Cancer Engineering Summit, a three-day event focusing on how engineering-driven innovation is reshaping the future of cancer research. A centerpiece of this year's meeting was the New Approach Methodologies (NAMs) Symposium, which highlighted emerging technologies designed to reduce reliance on animal testing while accelerating the path from discovery to patient care.

For decades, animal models have been a cornerstone of cancer research. Yet many therapies that appear promising in animals do not produce the same results in people. As cancer treatments become more targeted and biologically complex, researchers are increasingly turning to human-relevant systems that better replicate tumor biology and patient-specific responses.

The NAMs Symposium was the leadoff event at the summit, convening leaders from government, academia and industry to explore how advanced laboratory platforms, biomaterials, computational modeling and artificial intelligence are modernizing preclinical research. These approaches aim to improve predictive accuracy, lower development costs, shorten timelines to clinical trials and significantly decrease the use of animals.

The chair of the Bioengineering Department at Moffitt Cancer Center develops three-dimensional engineered tumor systems that re-create key features of human cancers in the laboratory. Unlike traditional two-dimensional cell cultures or some animal models, these 3D platforms allow researchers to study how cancer cells interact with surrounding tissue and immune cells. The team also designs biomaterial-based platforms that mimic the physical and mechanical properties of human tissue, enabling more realistic testing of cancer therapies. By evaluating drug response and resistance in these engineered systems, researchers can identify promising treatments earlier and potentially reduce costly late-stage clinical failures.

The NAMs Symposium was co-hosted by the vice president of portfolio strategy in Moffitt's Innovation and Entrepreneurship Office, who emphasized the broader strategic importance of the event. Moffitt expects to lead in this space from an oncology perspective, and the institution is working to bring people together to surface the field-shaping questions that will set the agenda for everyone working to develop more and better cures for cancer.

Looking ahead, speakers emphasized that engineering collaboration will be essential to fabricating, scaling and manufacturing realistic NAMs platforms. The director of the National Institute of Biomedical Imaging and Bioengineering at NIH highlighted the importance of cross-disciplinary expertise to move these technologies from proof-of-concept systems into scalable research tools. Future advancements may include integrating advanced sensors and imaging technologies with fluid and process engineering to create feedback-controlled systems capable of monitoring tumor behavior in real time.