Female Pancreatic Cancer Patients May Benefit from New Immunotherapy Approach

Highlights :

Female pancreatic cancer patients have immune cells that promote tumor growth and suppress the immune system more than male patients
Researchers found thatprotein called FPR2 causes immune suppression in female patients
Blocking FPR2 with a specific drug canimprove the ability of the immune system to fight the tumor in females, leading to new, sex-specific immunotherapy treatments

New research from Karolinska Institutet, Karolinska University Hospital, has discovered that sex can play a significant role in how the immune system responds to pancreatic cancer. The study found that in female mice, a specific protein called FPR2 can create an immune environment that allows cancer to grow and prevents immune cells from attacking it. This effect was not seen in male mice.

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‘Blocking a specific protein — FPR2 with a drug can improve the immune system of female pancreatic cancer patients, potentially paving the way for sex-specific immunotherapy treatments for the disease.’

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Mysteries of the Tumor Microenvironment

Pancreatic cancer is a highly aggressive and deadly disease, with a five-year survival rate of only 10% (). The tumor microenvironment plays a critical role in tumor progression and response to immunotherapy ().

Recent studies have shown that sex differences in the immune system can affect tumor progression and the landscape of the tumor microenvironment (). Therefore, a deeper understanding of sex-specific differences in the tumor microenvironment is needed to improve sex-optimized immunotherapy treatments (,, ).

The present study used advanced genetic techniques like single-cell RNA analysis and protein analysis to look at individual cells within the tumor and found a specific type of immune cell called a myeloid cell that was associated with this immune-suppressive effect in females. This myeloid cell was also linked to a poor prognosis in female patients with pancreatic cancer ().

The researchers found that FPR2, a protein that is involved in the regulation of inflammation, plays a key role in shaping the immune-excluded microenvironment of pancreatic tumors. They also discovered that FPR2 is involved in driving T-cell exhaustion, which is a state where T-cells become less effective at attacking cancer cells ().

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Tumor-Specific Sex Differences in the Immune System

Interestingly, the researchers found that the effects of FPR2 on the immune system were sex-dependent. Female mice with pancreatic tumors had a stronger immune response than male mice, and this was associated with differences in the expression of FPR2.

The researchers found that by blocking FPR2 in these immune cells, they could reverse the immune-suppressive effect and allow immune cells to attack the cancer. They also discovered that treatment with anti-TIM3 antibodies, a protein found on T cells, could further stimulate the immune response and help to kill the cancer cells.

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Breaking the Gender Barrier

Hence, understanding the role of FPR2 in shaping the tumor microenvironment and driving T-cell exhaustion may helpdevelop new therapies to target this protein, therebyimproving the effectiveness of immune-based treatments for pancreatic cancer.

“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 tumor development in different ways in male and female cancer patients with the goal to find and develop immunotherapy targets for each group.”

The study is the result of a close collaboration between Dr. Sarhan’s research group and researchers at Karolinska Institutet, Karolinska University Hospital, Pronoxis AB, and Uppsala University in Sweden and universities in Canada, Singapore, and China.

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Unlocking the Potential of Sex-Specific Immunotherapy

This study identified an immunosuppressive function of FPR2 in females, highlighting a potential sex-specific precision immunotherapy strategy for pancreatic cancer. Targeting FPR2 and its downstream signaling pathways may enhance the efficacy of immunotherapy in female patients with pancreatic cancer.

Further studies are needed to confirm the clinical relevance of these findings and to develop sex-optimized immunotherapy treatments.

The study suggests that FPR2 could be a target for new, sex-specific immunotherapies for pancreatic cancer.

By understanding the differences in how the immune system responds to cancer in males and females, doctors may be able to tailor treatments to individual patients and improve outcomes.

References:

Inflammatory Mechanisms Contributing to Pancreatic Cancer Development - (https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1360122/)
FPR2 Shapes an Immune-Excluded Pancreatic Tumor Microenvironment and Drives T-cell Exhaustion in a Sex-Dependent Manner - (https://aacrjournals.org/cancerres/article-abstract/doi/10.1158/0008-5472.CAN-22-2932/726286/FPR2-Shapes-an-Immune-Excluded-Pancreatic-Tumor)
Survival Rates for Pancreatic Cancer - (https://www.cancer.org/cancer/types/pancreatic-cancer/detection-diagnosis-staging/survival-rates.html)
Tumor microenvironment participates in metastasis of pancreatic cancer - (https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6065152/)

Source-Medindia