A New Hope for Pancreatic Cancer: Why Adding Immunotherapy Before Surgery Is Changing the Game

Pancreatic cancer has historically been one of the deadliest cancers, but a groundbreaking UCLA study is offering new hope by showing that adding immunotherapy to standard chemotherapy before surgery is safe and produces remarkable results in some patients. Researchers found that while the combination didn't create a clear survival advantage for most patients, a notable subset experienced unusually deep and durable responses, with some achieving complete tumor disappearance.

What Did the Study Actually Test?

A team at UCLA Health's Jonsson Comprehensive Cancer Centre conducted a clinical trial with 28 patients who had borderline-resectable pancreatic cancer—meaning surgery was technically possible but challenging. Patients received modified FOLFIRINOX chemotherapy (a standard multi-drug combination) combined with nivolumab, an immunotherapy drug that works by releasing the brakes on the immune system so it can attack cancer cells more effectively.

The researchers had a unique advantage: they could directly examine tumor tissue removed during surgery and compare it with samples taken before treatment. This allowed them to understand exactly how the combination therapy changed the tumor's immune environment—something rarely studied in pancreatic cancer.

Which Patients Benefited Most?

The results revealed a striking pattern. Most patients tolerated the combination well and were able to proceed to surgery, with no serious immune-related side effects. Here's what happened:

• Surgical Success Rate: 79% of patients went on to surgical resection, and all patients who underwent surgery had their tumors successfully removed with clean margins in 86% of cases
• Lymph Node Response: 50% of patients had no cancer detected in their lymph nodes, a critical indicator of disease spread
• Complete Responses: 9% experienced complete disappearance of detectable cancer at the time of surgery, while another 9% had near-complete responses

While these complete responses represent a small percentage, they're significant because pancreatic cancer rarely produces such dramatic results. For context, overall survival outcomes were similar to chemotherapy alone for most patients, but the subset with deep responses showed unusually durable disease control.

Why Doesn't Immunotherapy Work Better in Pancreatic Cancer?

The study revealed something crucial: immunotherapy did activate immune cells within tumors, including higher levels of cancer-killing CD8 T cells. However, the treatment also triggered unexpected changes that may explain why immunotherapy often fails in pancreatic cancer.

The immune cells became disorganized, clustering in ways that reduced their effectiveness. Additionally, the treatment led to an accumulation of exhausted T cells—immune cells that are activated but too worn out to attack cancer effectively. "By testing this novel drug combination in the preoperative setting, we were able to directly compare pre-treatment biopsies with surgical resection specimens to better understand why the therapy works in some patients, and, just as importantly, why it does not in others, and what additional strategies might improve responses," said Dr. Timothy Donahue, chief of surgical oncology at UCLA's David Geffen School of Medicine.

These insights are valuable because they point to specific problems researchers can now target. Future treatments might focus on preventing immune exhaustion or improving immune cell organization to help more patients achieve the kind of responses seen in that 9% subset.

What Happens Next?

This study establishes a new platform for testing pancreatic cancer treatments in a systematic way. Rather than simply measuring survival, researchers can now examine how treatments reshape the tumor's immune landscape—information that could guide the development of more effective, personalized strategies.

The findings suggest that immunotherapy may benefit select patients with pancreatic cancer, but identifying who those patients are remains the key challenge. Researchers are now focused on developing better ways to predict which patients will respond and creating combination strategies that address the immune exhaustion problem the study revealed.

For patients with borderline-resectable pancreatic cancer, this research offers cautious optimism. While immunotherapy plus chemotherapy isn't a cure-all, it's safe, helps patients reach surgery, and produces remarkable responses in some individuals—making it a promising avenue worth exploring as treatment options continue to evolve.