Immunotherapy Shows Promise for Pancreatic Cancer Treatment

A fresh study from UCLA Health Jonsson Comprehensive Cancer Center indicates that adding immunotherapy to standard chemotherapy before surgery is safe and demonstrates potential benefits for some patients with borderline-resectable pancreatic cancer, a historically challenging disease to treat. The findings, published in Nature Communications, offer a glimmer of hope for a cancer with limited effective treatment options.

Understanding the Challenge of Pancreatic Cancer

Pancreatic cancer remains one of the deadliest cancers, with few effective treatment options and historically limited responses to immunotherapy, a treatment that has revolutionized care for other cancer types like lung and breast cancer. Researchers have been exploring whether combining immunotherapy with chemotherapy before surgery could improve outcomes, but this strategy hadn’t been extensively tested in pancreatic cancer until now.

The UCLA Study Design

Researchers conducted a Phase 1b/2 clinical trial involving 28 patients with borderline-resectable pancreatic cancer. These patients received modified FOLFIRINOX chemotherapy in combination with the immunotherapy drug nivolumab prior to surgery. This approach allowed for direct analysis of tumor tissue before and after treatment, comparing it to historical samples from patients who received chemotherapy alone. Advanced techniques, including gene expression analysis, immunohistochemistry, and spatial transcriptomics, were used to examine how the treatment altered the tumor’s immune landscape.

Key Findings of the Trial

• Surgical Resection Rates: 79% of patients were able to undergo surgical resection after the treatment.
• Successful Tumor Removal: All patients who underwent surgery had their tumors successfully removed.
• Clean Margins: 86% of patients achieved clean surgical margins, meaning no cancer cells were found at the edges of the removed tissue.
• Lymph Node Status: 50% of patients had no cancer detected in their lymph nodes.
• Durable Responses: While overall survival outcomes were similar to those achieved with chemotherapy alone, a subset of patients experienced significant benefits:
• 9% experienced a complete disappearance of detectable cancer at the time of surgery.
• Another 9% had near-complete responses.
• Immune System Changes: Immunotherapy increased immune activity within tumors, including higher levels of cancer-killing CD8 T cells. However, the treatment also led to changes in the tumor immune environment, characterized by disorganized immune cell clusters and an accumulation of plasma cells and exhausted T cells, potentially limiting long-term tumor control.

Implications for Future Treatment

Whereas adding immunotherapy to standard chemotherapy didn’t provide a clear survival advantage for all patients with borderline-resectable pancreatic cancer, the study highlights the potential for benefit in select individuals. The research also provides valuable insights into why immune-based treatments have had limited success in pancreatic cancer, suggesting that while immunotherapy can activate immune cells, it may also disrupt immune organization and promote immune exhaustion.

“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 and professor of surgery at the David Geffen School of Medicine at UCLA.

Future research will focus on identifying patients most likely to benefit from this combination therapy and developing strategies to enhance sustained anti-tumor immune responses. Researchers are also exploring other immunotherapies, including a novel “one-product-fits-all” CAR-NKT cell therapy developed at UCLA, which aims to overcome the challenges of treating solid tumors like pancreatic cancer. This therapy uses engineered immune cells that can be mass-produced and is significantly more affordable than current personalized cell therapies.

Investigators from the UCLA Health Jonsson Comprehensive Cancer Center have also been awarded a $4 million grant from the National Cancer Institute to further advance immune-based therapies for pancreatic ductal adenocarcinoma.