Immunotherapy has limited effect for pancreatic cancer, and differs between men and women. A new study published in Cancer Research reveals certain immune cells in women with pancreatic cancer that, instead of fighting the tumour, interferes with the body’s immune response. These findings may pave the way for a more sex-specific treatment.
“More and 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,” says the paper’s first author Fei He, former visiting researcher at Karolinska Institutet. “Our results provide new perspectives that can have high impact on the treatment of cancer.”
In recent years, immunotherapy, which stimulates the immune system to attack cancer cells, has contributed significantly to the treatment of different kinds of cancer, such as melanoma and lung, kidney and liver cancer. However, it is much less effective against pancreatic cancer, which remains one of the deadliest kinds of cancer that leaves patients, on average, with four to six months left to live after diagnosis.
Sex-biased differences in the immune response
Previous studies have shown that there are sex-bound biological differences in the male and female immune system that, amongst other effects, determine how tumours grow and the body’s ability to defend itself against them. The present study addressed what might cause such sex-related disparities in the immune response to pancreatic cancer.
The study revealed the presence of a subpopulation of myeloid cells in women that protect the tumour and prevents the immune system’s T cells from infiltrating the tumour and attacking the cancer cells.
“This sub-group of immune cells correlates with poor survival exclusively in female cancer patients,” says the study’s corresponding author and principal investigator Dhifaf Sarhan, assistant professor at the Department of Laboratory Medicine, Karolinska Institutet. “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.”
New target for immunotherapy in women
The results can be useful to the development of diagnostic tools and immunotherapy for pancreatic cancer that take into account biological differences between men and women. The study used a combination of methods including single-cell RNA sequencing, proteomics, test tube and patient validation, and treatments of 3D pancreatic cancer models and mice.
“The next step is to follow up our new immunotherapy target for women,” says Dr Sarhan. “We’re also performing extensive analyses to understand how immunological sex differences drive tumour development in different ways in male and female cancer patients with the goal to find and develop immunotherapy targets for each group.”
Source: Karolinska Institutet
