Researchers from Karolinska Institutet have found that certain immune cells in women with pancreatic cancer can obstruct their immune response.
The findings may explain differences in the effects of pancreatic cancer in men and women and pave the way for more sex-specific treatment options. The disease can be effectively treated through immunotherapy; however, the effects of the treatment vary between men and women.
The study, titled ‘FPR2 shapes an immune-excluded pancreatic tumour microenvironment and drives T-cell exhaustion in a sex-dependent manner’, has been published in the journal Cancer Research.
“More evidence is coming in that male and female hormones affect our immune system, but much remains to be done before sex can be included as a self-evident biological factor in medical research and therapy,” said Fei He, first author of the study and researcher at the Department of Laboratory Medicine, Karolinska Institutet.
“Our results provide new perspectives that can have a high impact on cancer treatment,” he added.
Immunotherapy for pancreatic cancer is limited
Immunotherapy has significantly improved the treatment of cancers such as melanoma and lung, liver, and kidney cancer over recent years; however, it is less effective against pancreatic cancer. Pancreatic cancer is one of the deadliest cancers, and patients are typically given four to six months to live after diagnosis.
Past research has found sexual biological differences in male and female immune systems can determine how tumours grow and the body’s ability to defend itself against them.
Creating targeted therapy for women
The Karolinska Institutet researchers have identified a crucial difference in tumour properties in men and women with pancreatic cancer. They found an immune cell present only in women that protects the tumour and prevents the T cells from penetrating the tumour and attacking cancer cells.
“This sub-group of immune cells correlates with poor survival exclusively in female cancer patients. Our results show that the immune cells express a specific protein called FPR2 and can serve both as a sex-specific prognostic factor and a therapeutic target,” explained Dhifaf Sarhan, assistant professor at the Department of Laboratory Medicine, Karolinska Institutet.
The researchers based their study on a combination of methods, including single-cell RNA sequencing, proteomics, test tube and patient validation, and treatments of 3D pancreatic cancer models and mice. They hope their findings can inform the development of new diagnostic tools and immunotherapies for pancreatic cancer that consider sex-specific differences.
“The next step is to follow up on our new immunotherapy target for women. We’re also performing extensive analyses to understand how immunological sex differences drive tumour development in different ways in male and female cancer patients to find and develop immunotherapy targets for each group,” concluded Sarhan.
