Williams Cancer Institute

Unveiling the Dual Role of Neutrophils in Lung Cancer Progression

Lung cancer continues to be a major global health issue, causing the highest number of cancer-related deaths worldwide. Central to the development of lung cancer is the tumor microenvironment, which involves complex interactions with immune cells, including neutrophils. Initially considered beneficial due to their anti-tumor activities in early cancer stages, neutrophils are now recognized to play a dual role, potentially enhancing cancer metastasis influenced by the tumor surroundings.

A pioneering study from Xuzhou Medical University, published in the journal *Cancer Biology & Medicine*, reveals a novel mechanism by which neutrophils accelerate lung cancer progression. This research highlights the crucial role of neutrophils—typically the first responders to inflammation—as they take on pro-tumoral roles within the cancer microenvironment, significantly influencing cancer metastasis dynamics.

The study investigates the roles of the PARP-1/Alox5/MMP9 axis in regulating lung cancer-associated neutrophil activation, thus promoting lung cancer progression. Activated by lung cancer cells, neutrophils engage PARP-1, which subsequently collaborates with another protein, ALOX5. This interaction is vital as it enhances the production of MMP-9, an enzyme essential for degrading tissue structures and promoting cancer invasion and metastasis.

Using techniques such as immunohistochemistry, the researchers examined neutrophil infiltration in lung cancer tissues and employed in vitro assays to analyze their impact on lung cancer cell behaviors. Gene knockdown and pharmacological inhibition of PARP-1 further elucidated its role in this process. Supported by validation in mouse models, the results indicate that blocking PARP-1 could significantly reduce tumor growth, shedding light on the complex relationship between the immune system and cancer.

Dr. Junnian Zheng, the lead author of the study, comments, “This research not only enhances our understanding of the biological interactions between lung cancer cells and neutrophils but also paves the way for new targeted therapies that could disrupt these interactions and potentially improve patient outcomes.”

These findings suggest that targeting the PARP-1-ALOX5-MMP-9 pathway might be a promising approach to suppress the tumor-promoting activities of neutrophils in lung cancer. This strategy could lead to innovative therapies that slow lung cancer progression and enhance the effectiveness of current treatments. By focusing on the interplay between neutrophils and lung cancer cells, researchers are opening new avenues for treatment that could significantly impact the future of lung cancer therapy.

The dual role of neutrophils in lung cancer highlights the complexity of the tumor microenvironment and the need for targeted therapeutic strategies. The insights from this study provide a deeper understanding of how neutrophils can both fight and fuel cancer, offering hope for more effective treatments that can better manage and potentially cure lung cancer.

Reference: Lulu Han, Yuxin Chen, Nan Huang, Xiaowan Zhou, Yanfang Lv, Huizhong Li, Dafei Chai, Junnian Zheng and Gang Wang, https://www.cancerbiomed.org/content/early/2024/01/02/j.issn.2095-3941.2023.0248

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