Researchers from Johns Hopkins Medicine have discovered that the organization of different types of immune cells within pancreatic tumors is associated with how well patients with pancreatic cancer respond to treatment and how long they survive. The new findings, published Sept. 16 in Cancer Research, could eventually lead to new ways of treating pancreatic cancer, which has the highest mortality rate of all major cancers.
In 2022, the National Cancer Institute estimates that more than 62,000 Americans are expected to be diagnosed with pancreatic cancer and nearly 50,000 will die from the disease. On average, only about 10% of people with pancreatic cancer will survive for five years. Predicting which patients are most likely to respond to the few existing treatments is difficult; researchers have long been searching for more tools — cells, molecules or genes — that stratify pancreatic cancer patients by survival.
In recent years, scientists studying many types of cancer have discovered the importance of the noncancerous cells, molecules and blood vessels surrounding tumors — called the tumor microenvironment. Part of this tumor microenvironment is immune cells; some have the ability to target a tumor for destruction while others help the tumor evade the immune system.
Researchers at Oregon Health & Science University used a method called multiplexed immunohistochemistry to pinpoint the locations of 27 different immune molecules in surgically resected tumors from 45 people with pancreatic ductal adenocarcinoma — the most common form of pancreatic cancer. The patients were 52% women, a median of 63.5 years old, and had all stages of cancer, with 41% of participants’ cancer spread to at least four lymph nodes.
The molecules — found in different combinations on the surface of different immune cell types — correspond to the relative locations of subtypes of immune cells.
Then, they developed new computational algorithms to analyze how these cells, in number, location and shape, varied between patients who survived longer or shorter than the median survival time of 619 days.
The researchers discovered that, among the 22 patients who survived shorter than average (a median of 313 days), immune cells called IL-10+ myelomonocytes tended to be located close to a cluster of granzyme B+ CD8+ T cells (or cytotoxic T lymphocytes). Among the 23 patients who survived longer than average (a median of 832 days), the same myelomonocytes were more grouped near a different type of T cell, known as PD-1+ CD4+ T cells (or activated helper T cells).
