Pancreatic cancer may begin hiding from the immune system earlier than we thought

(Press-News.org) A new study suggests that pancreatic cancer may start preparing to “hide” from the immune system long before the disease becomes full-blown cancer. Researchers found that very early, precancerous cells in the pancreas don’t spread randomly, they gather into specific clusters and create small “neighborhoods” inside the tissue. These early cell groups also seem to communicate directly with nearby immune cells in ways that may weaken the body’s ability to fight them. Using advanced tools that characterize cells at the molecular level in tissue section of the pancreas, the team discovered that immune-suppressing signals appear at these early stages, meaning the cancer may begin escaping immune detection much sooner than previously assumed. The findings could help scientists develop better ways to spot pancreatic cancer earlier.

A new study from researchers at the Hebrew University of Jerusalem provides fresh insight into how pancreatic cancer may begin taking shape years before it is clinically detected. The research shows that early precancerous pancreatic cells organize into distinct spatial “niches” and engage in targeted interactions with immune cells, potentially creating an immunosuppressive environment at the very earliest stages of disease development.

The study, led  Dr. Oren Parnas and carried out by the student Sebastian Arcila-Barrera with the help of Dr. Sharona Tornovsky-Babeay in the Faculty of Medicine at the Hebrew University of Jerusalem, combined single-cell RNA sequencing with spatial transcriptomics to examine pancreatic tissue samples. By preserving the spatial context of thousands of individual cells, the researchers were able to map how different types of acinar metaplastic cells organize within premalignant lesions and how they interact with surrounding immune cells.

Pancreatic ductal adenocarcinoma is among the deadliest forms of cancer, largely due to late diagnosis and limited treatment options. Although precancerous lesions can exist for a decade or more before invasive cancer develops, little is known about how these early cellular changes are structured or how they influence the local tissue environment.

“Our findings show that these early altered cells are not randomly distributed,” said Dr. Parnas. “Instead, cells with similar identities tend to cluster together, forming semi-homogeneous niches that appear to actively interact with specific immune cell populations.”

The study revealed that certain metaplastic cell states are consistently found in close proximity to immune cells associated with immune suppression, including specific subsets of neutrophils and macrophages. These interactions were linked to gene expression patterns known to dampen immune activity, suggesting that immune evasion may begin well before cancer becomes invasive.

Sebastian Arcila-Barrera noted that the organization of these cells provides important clues about disease progression. “The spatial patterns we observed suggest that cell identity is established early, followed by localized expansion,” he explained. “This helps clarify how premalignant lesions develop and evolve over time.”

Dr. Sharona Tornovsky-Babeay emphasized the translational importance of the findings. “Understanding the process of lesion formation and development, we may be able to better identify high-risk lesions and, in the future, design strategies that intervene before cancer fully develops,” she said.

Importantly, the researchers observed similar cellular organizations and immune interactions in human pancreatic tissue, strengthening the relevance of the findings beyond animal models.

Together, the results offer a more detailed picture of the earliest events in pancreatic cancer initiation and highlight how spatial organization and immune interactions may shape disease outcomes long before symptoms appear.

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