"New Research Reveals Unexpected Links Between Leukemic Cells and Immune Cells"
Credit: medicalxpress
🔸STAT3's Role in Identifying Leukemic Cells :
The protein STAT3 plays a crucial role in helping the immune system recognize leukemic cells. This understanding is essential for advancing future immunotherapy. Researchers at the Carl Landsteiner University of Health Science have made this significant discovery.
Their findings show that STAT3 influences the surface characteristics of leukemic cells, making them more detectable by the immune system. When this process is disrupted, leukemic cells can escape immune surveillance. The expression and surface features of STAT3 on leukemic cells could be key markers for developing new immunotherapy approaches.
🔸 Enhancing Immunotherapy :
Improving the relapse rate can significantly enhance the effectiveness of immunotherapy, enabling the body's immune system to target and eliminate residual cancer cells. This method activates lymphocytes to attack and destroy virus-infected tumor cells.
🔸 AML Cells' Response :
AML cells often evade the immune system, and understanding this evasion is crucial for improving immunotherapy's effectiveness. The research conducted by the KL Krems team has made notable progress in this area and has been published in Frontiers in Immunology.
🔸Efficient Elimination :
Dr. Dagmar Stoiber-Sakaguchi explains that this study is the first to show how STAT3 enhances the elimination of leukemic cells by NK cells. This improvement is due to an interaction with a surface structure on AML cells called ICAM-1. AML cells lacking STAT3 are less effectively eliminated by NK cells, particularly when ICAM-1 levels are also low.
ICAM-1, an intercellular adhesion molecule, serves as a crucial binding site for NK cells, which are essential for destroying cancer cells. Low levels of ICAM-1 hinder the NK cells' ability to function properly.
🔸 Detailed Mechanism :
NK cells form immune synapses with ICAM-1 on leukemic cells, through which cytotoxic molecules are transferred, leading to the destruction of cancer cells. This process is inefficient without STAT3, allowing AML cells to evade immune defenses.
🔸Rigorous Testing :
To validate their findings, Stoiber-Sakaguchi's team modified STAT3-deficient AML cells to produce ICAM-1, compensating for the lack of STAT3 and improving NK cell-mediated elimination. This suggests that STAT3, in conjunction with ICAM-1, sensitizes leukemic cells to the immune system.
Further research on patient data from the Medical University of Graz confirmed that STAT3 and ICAM-1 expression levels are positively correlated in AML cells. Higher STAT3 levels led to increased ICAM-1 production.
🔸 Patient Outcomes :
Dr. Agnieszka Vitalis-Cipraká, the study's first author, noted that patients with higher ICAM-1 expression had longer survival rates, likely due to more effective AML cell elimination by NK cells.
Prof. Stoiber-Sakaguchi stated, "We are pleased to contribute to the understanding of how AML cells can evade the body's immune defenses. The expression of STAT3/ICAM-1 could be a potential biomarker for personalizing future immunotherapy."