How the immune system influences pancreatic cancer

The challenge: Pancreatic cancer's complexity

One of the reasons pancreatic cancer is so difficult to treat is due to its heterogeneity - the significant variability that exists within each tumour. This means a single tumour can contain different subtypes, making it difficult to target with existing treatments. Two key subtypes, the classical (CLA) and basal-like (BL) forms, play a crucial role in the disease's progression. When both are present, survival rates decline and treatment becomes even more challenging.

A breakthrough in understanding the immune system's role

A team led by Dr. Shiv K. Singh at UMG has now discovered that immune cells, particularly macrophages, play a pivotal role in the way pancreatic tumours evolve. Macrophages are immune cells that typically help the body fight infections and diseases. However, in pancreatic cancer, these cells are drawn to the tumour by specific signals and then manipulated to suppress the body's natural immune response. Instead of helping to destroy the tumour, they actually weaken the immune system's ability to fight back.

By altering the activity of cytotoxic T cells - the "killer cells" of the immune system—pancreatic tumours can grow unchecked. This discovery highlights how the tumour actively creates an environment where it can thrive, rather than being attacked by the body's defences.

Targeting the tumour’s "Immune Shield"

This research has identified a key inflammatory protein, TNF-α, which is secreted by macrophages and plays a major role in helping pancreatic tumours evade the immune system. Tumours essentially "hijack" this protein to suppress immune responses that would otherwise keep them in check.

New hope: A potential game-changer in treatment

The research team is now developing new treatment strategies to target this process. By combining immunotherapy with chemotherapy, they hope to counteract the harmful effects of TNF-α-producing macrophages while restoring the immune system’s ability to fight the disease.

Initial tests in preclinical models have shown promising results, with reduced inflammation in the tumour and improved survival rates. The next step will be clinical trials to determine how these findings can be translated into new therapies for people living with pancreatic cancer.

Why this matters

Immunotherapy has shown great promise in treating various cancers, offering new hope for patients. However, pancreatic cancer has remained particularly difficult to treat with this approach due to its highly complex and immune-suppressive tumour environment. Advances in our understanding of pancreatic cancer and its interactions with the immune system are essential for overcoming these challenges. By identifying new mechanisms and immune targets, we can develop smarter, more targeted therapies that may finally unlock the potential of immunotherapy for this disease.

At Pankind, we are committed to driving research that leads to real, life-changing progress. This study reinforces the importance of funding innovative research to improve treatment options and, ultimately, survival rates.

Reference: Klein et al, Nature Communications (2025). DOI: 10.1038/s41467-024-55330-7