Study Finds Neutrophils Shape Cancer Outcomes by Switching Roles Within Tumors

Neutrophils, the most plentiful white blood cells in the body, have recently emerged as significant players in cancer, far beyond their classical role in immune defense. Once regarded simply as front-line responders to infection, these cells are now known to possess a complex, dual nature within the tumor environment. As explained in a review from Zhejiang University and Wenzhou Medical University published in Cancer Biology & Medicine, neutrophils can either foster or hinder tumor growth, depending on signals from their surroundings. 

The review discusses how tumor-associated neutrophils (TANs) adapt to conditions within tumors and can change their function. This adaptability, or plasticity, means neutrophils may support cancer through angiogenesis—the creation of new blood vessels—suppress immune responses, and facilitate cancer’s spread to other organs. Conversely, under specific circumstances, they can also help destroy tumor cells and back up other immune cells such as T cells.

This complexity originates from the ability of neutrophils to polarize into different types: anti-tumor (N1) or pro-tumor (N2). Factors such as TGF-β, IL-6, and granulocyte-CSF (G-CSF), produced by the tumor, push neutrophils towards the N2 state, which is linked to immune suppression, increased blood vessel formation, and metastasis. On the other hand, cytokines like IFN-β and retinoic acid can drive neutrophils to adopt the N1 type, which enhances direct killing of tumor cells and strengthens immune surveillance. Besides, neutrophils can contribute to antibody-dependent destruction of tumor cells and, in certain settings, even present tumor antigens to the immune system.

The process by which neutrophils promote metastasis is particularly intricate. They help tumor cells survive as they travel through the body, encourage their implantation in distant organs, and prepare the tissues there to accommodate new cancer growth. Recognizing these activities, new therapies are being developed to alter neutrophil function or block their recruitment to tumors. Inhibitors of CXCR2 and c-MET, as well as drugs targeting STAT3 or TGF-β, are showing promise in experimental studies and early clinical trials.

Despite this therapeutic potential, the short lifespan and dynamic nature of neutrophils present significant obstacles. As Chenghui Yang, the review’s corresponding author, stated, “Neutrophils are no longer seen as mere bystanders in cancer. Their dual nature makes them both a challenge and an opportunity in cancer therapy.”

Looking ahead, efforts to reprogram neutrophils or selectively block their tumor-promoting actions could improve cancer treatment. Strategies that prevent neutrophils from aiding the spread of cancer or that transform them into more active tumor-fighters may complement current immunotherapies. As researchers deepen their understanding of how neutrophils behave in various cancers and at different stages, the possibility of precision treatments that leverage or restrain these “double agents” of immunity edges closer to reality.