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Decoding Blood Cancer's Evasion Tactics: A Study on Immune System Resistance

Leukocytes, or white blood cells, play an important role in immune defence. Natural killer cells (NK cells) are also white blood cells. (Image: Mostphotos)

In a significant advancement in cancer research, a collaborative study between the University of Helsinki and the Dana-Farber Cancer Institute, Harvard Medical School, has unveiled how blood cancer cells manage to escape destruction by the immune system's natural killer (NK) cells. This breakthrough could lead to more effective cancer immunotherapies, addressing the limitations and side effects of existing T-cell therapies.

NK cells, crucial components of the immune system, patrol the body to identify and destroy cancerous or virally infected cells. Despite their pivotal role, cancer cells, particularly in blood cancers like leukemias, lymphomas, and myelomas, have developed sophisticated mechanisms to evade NK cells. Understanding these evasion strategies is critical to enhancing NK cell therapies and providing better treatment options for patients.

Physician-scientist Olli Dufva from the University of Helsinki emphasizes the need to thoroughly evaluate the resistance and sensitivity mechanisms to NK cell therapies in blood cancers. The research team utilized single-cell RNA sequencing to analyze gene activity in individual tumor and immune cells. This technique, considered the gold standard in cellular molecular analysis, reveals the active genes in each cell, providing insights into cellular states and interactions.

The study exposed various cancer types to NK cells in the lab, analyzing gene activity changes upon interaction. Results showed that NK cells responded differently to different cancer cells, with some inducing an active NK response while others elicited none. PhD Sara Gandolfi, involved in the research, highlighted these varying reactions, underscoring the complexity of the interaction between cancer and immune cells.

To identify potential therapeutic targets, the researchers employed the CRISPR-Cas9 gene-editing method to modify genes in cancer cells and determine which alterations increased their vulnerability to NK cell attack. This led to the identification of several genes involved in NK cell sensitivity and resistance, including known mechanisms like antigen presentation and new factors like adhesion-related glycoproteins.

Professor of Translational Hematology Satu Mustjoki (University of Helsinki and Helsinki University Hospital Comprehensive Cancer Center) points out the comprehensive nature of the study, providing valuable resources for developing personalized NK cell immunotherapies. Associate Professor Constantine Mitsiades (Dana-Farber Cancer Institute, Harvard Medical School) emphasizes the study's broad impact, shedding light on immunotherapy resistance across various cancer types.

This research, supported by grants from several foundations and institutions, including the Leukemia and Lymphoma Society and the Research Council of Finland, represents a crucial step in the fight against blood cancers. By uncovering the molecular dynamics of NK and cancer cell interactions, it opens new avenues for targeted, effective cancer treatments.

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