April 20, 2024

Scientists Uncover Potential Explanation for Sex Differences in Pancreatic Cancer

Immunotherapy has actually shown to be a successful treatment approach for numerous cancer types, however its effectiveness in pancreatic cancer is minimal and exhibits variations in between men and females. Scientists at the Karolinska Institute have possibly discovered the factor behind this gender inconsistency. Their research study, published in Cancer Research, recognizes an immune cell present in ladies with pancreatic cancer that impedes the bodys immune response. These findings could lead to the development of more customized, gender-specific treatments.
The study was moneyed by the Swedish Cancer Society, Karolinska Institute (KI Funds), the Centre for Innovative Medicine (CIMED) and the Cancer Research Funds of Radiumhemmet (see paper for complete list).

Pancreatic cancer is a frequently aggressive and formidable form of cancer that emerges in the pancreas, an important organ accountable for producing hormones and digestive enzymes. This disease is especially challenging to treat and detect, as it often goes undetected up until it reaches advanced phases.
Immunotherapy has actually proven to be a successful treatment method for numerous cancer types, but its efficacy in pancreatic cancer is minimal and exhibits disparities in between men and ladies. Their study, released in Cancer Research, determines an immune cell present in ladies with pancreatic cancer that prevents the bodys immune response.
” More and more evidence is can be found in that male and female hormonal agents impact our body immune system, however much remains to be done prior to sex can be consisted of as a self-evident biological aspect in medical research study and therapy,” says the papers very first author Fei He, a previous going to scientist at the Department of Laboratory Medicine, Karolinska Institute. “Our results offer brand-new point of views that can have a high impact on the treatment of cancer.”
Over the last few years, immunotherapy, which promotes the body immune system to attack cancer cells, has contributed considerably to the treatment of various kinds of cancer, such as melanoma and liver, kidney, and lung cancer. It is much less reliable against pancreatic cancer, which remains one of the most dangerous kinds of cancer that leaves clients, on average, with 4 to six months left to live after medical diagnosis.

Sex-biased distinctions in the immune reaction
Previous studies have actually revealed that there are sex-bound biological distinctions in the male and female body immune systems that, amongst other results, determine how tumors grow and the bodys ability to defend itself against them. A collaborative research study including researchers at Karolinska Institute in Sweden has now addressed what may cause such sex-related variations in the immune action to pancreatic cancer.
The research study demonstrated a vital distinction in tumor homes in males and women with pancreatic cancer. There is a type of immune cell present in females that secures the tumor and avoids the immune systems T cells from infiltrating the growth and assaulting the cancer cells.
” This sub-group of immune cells correlates with bad survival exclusively in female cancer clients,” says the research studys matching author and primary investigator Dhifaf Sarhan, assistant teacher at the Department of Laboratory Medicine, Karolinska Institute. “Our results show that the immune cells reveal a specific protein called FPR2 and can serve both as a sex-specific prognostic element and a restorative target.”
New target for immunotherapy in ladies
The results can be helpful to the development of diagnostic tools and immunotherapy for pancreatic cancer that take into account biological differences in between males and females. The study was based on a combination of techniques consisting of single-cell RNA sequencing, proteomics, test tube and client recognition, and treatments of 3D pancreatic cancer models and mice.
” The next step is to follow up our new immunotherapy target for ladies,” states Dr. Sarhan. “Were likewise performing extensive analyses to understand how immunological sex distinctions drive tumor advancement in different ways in female and male cancer patients with the goal to discover and establish immunotherapy targets for each group.”
Reference: “FPR2 shapes an immune-excluded pancreatic tumor microenvironment and drives T-cell fatigue in a sex-dependent manner” by Fei He, Apple H.M. Tay, Ahmed Calandigary, Enana Malki, Sayaka Suzuki, Tianjie Liu, Qi Wang, Carlos Fernández-Moro, Marina Kaisso, Peter Olofsson‐Sahl, Marit Melssen, Siu Kwan Sze, Mikael Björnstedt, Matthias J. Löhr, Mikael C.I. Karlsson, Rainer Heuchel and Dhifaf Sarhan, 15 March 2023, Cancer Research.DOI: 10.1158/ 0008-5472. CAN-22-2932.
The research study is the result of a close collaboration between Dr. Sarhans research group and scientists at Karolinska Institute, Karolinska University Hospital, Pronoxis AB, and Uppsala University in Sweden and universities in Canada, Singapore, and China.
The study was funded by the Swedish Cancer Society, Karolinska Institute (KI Funds), the Centre for Innovative Medicine (CIMED) and the Cancer Research Funds of Radiumhemmet (see paper for complete list). Peter Olofsson‐Sahl operates at Pronoxis, which establishes villains for FPR1 and FPR2. The other researchers report no conflicts of interest.