Neutrophils can enhance the efficacy of cancer immunotherapy

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Neutrophils can enhance the efficacy of cancer immunotherapy

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Neutrophils can enhance the efficacy of cancer immunotherapy. 

For a long time, cancers have been an insurmountable hurdle in the medical field.

Fortunately, in recent years, the rise of cancer immunotherapy has brought new hope to cancer patients.

This cutting-edge therapy works by activating a cancer patient’s immune system and prompting it to clear the tumor on its own.

Unfortunately, although cancer immunotherapy has been shown to elicit durable antitumor responses, it is only effective in a minority of patients. This phenomenon shows that there must be some key factors affecting cancer immunotherapy in the human body that have not been discovered.

On March 30, 2023, scientists from the University of Geneva, Switzerland, Harvard Medical School, and the Ludwig Institute for Cancer Research published a paper titled: A neutrophil response linked to tumor control in immunotherapy (related to tumor control in immunotherapy) in the journal Cell neutrophil response) research paper.

The study analyzed the role of neutrophils in cancer immunotherapy and found that neutrophils play more than one role in cancer. Depending on the molecular markers on their surface, these neutrophils can either promote tumor growth or inhibit tumor progression.

Therefore, by altering these molecular markers, neutrophils can become important players in anti-tumor immunity, enhancing the efficacy of cancer immunotherapy and ensuring the success of treatment.

Neutrophils , the most abundant immune cells in the blood, are very useful during infection or injury because they can be quickly mobilized to the affected area and release antimicrobial factors.

However, their presence is usually bad news in the context of cancer, as they promote vascularization and tumor progression.

Notably, recent high-dimensional single-cell analyzes revealed that circulating and tumor-infiltrating neutrophils exhibit heterogeneity in transcriptome and surface protein expression levels.

This heterogeneity raises the question—are phenotypically distinct neutrophils present in tumors with opposite functional activities? Do these tumor-infiltrating neutrophils have unexpected antitumor efficacy?

To understand the exact role of neutrophils in cancer, the research team performed cancer immunotherapy in tumor-bearing mice with lung or colorectal cancer and observed changes in neutrophils.

It was found that in the tumor-bearing mice that responded well to the treatment, the number of neutrophils increased significantly.

Neutrophils accumulate in tumors in the context of successful treatment

This result contradicts what was previously known about the role of neutrophils in cancer, and prompted the research team to further explore why.

So the research team devised new experimental protocols to compare successful and unsuccessful cancer immunotherapies, and then analyzed individual cells of interest in more detail.

The research team found that in tumor-bearing mice, immunotherapy-induced neutrophils acquired the interferon gene.

The same thing has been observed in cancer patients and appears to be crucial for the success of the therapy — loss of the interferon-responsive transcription factor IRF1 in neutrophils leads to immunotherapy failure.

In addition, neutrophil responses depended on key components of antitumor immunity, including BATF3-dependent human dendritic cells, IL-12, and IFNγ.

Immunotherapy-induced neutrophils acquire an interferon-stimulated gene signature

Further analysis revealed that neutrophils are actually much more diverse than previously thought and carry different markers, some of which carry specific molecular markers that have anti-tumor efficacy .

What’s more, when the researchers blocked these specific neutrophil responses, the benefits of the treatment disappeared.

These results suggest that neutrophils can be divided into two classes in terms of their interactions with tumors— pro-tumor and anti-tumor .

Interestingly, anti-tumor neutrophils also appear to have the same potent cytotoxicity, or ability to destroy other cells, as neutrophils that fight bacterial infection or repair wounds.

Therefore, their ability to produce and release cytotoxic molecules may have antitumor therapeutic implications.

Immunotherapy-induced neutrophils exhibit distinct phenotypes and maturation states

Professor Mikael J. Pittet , the corresponding author of the paper , said: Neutrophils are first produced in the bone marrow and then circulate in the blood and tissues.

Thus, the fate of pro-tumor or anti-tumor neutrophils appears to have been determined in the bone marrow. From this point of view, if we can manipulate this process, can we train a strong army against tumors?

Research Model Diagram

Altogether, this latest study, published in Cell , demonstrates that neutrophils are heterogeneous and that some special types of neutrophils have powerful anti-tumor functions.

These promising results show that neutrophils can be mobilized to fight cancer, making current cancer immunotherapies more effective and opening the way for new treatments!

Paper link :

www.cell.com/cell/fulltext/S0092-8674(23)00210-6

Neutrophils can enhance the efficacy of cancer immunotherapy

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