Research finds neutrophils produce CCL3, promoting tumor growth in various cancers — Evidence Review
Published in Cancer Cell, by researchers from University of Geneva, Ludwig Institute for Cancer Research
Researched by
— the AI search engine for science
Table of Contents
Neutrophils, a type of immune cell, can be reprogrammed by the tumor environment to produce the chemokine CCL3, which promotes tumor growth—a finding from researchers at the University of Geneva. Most related studies support the idea that neutrophils have dual roles in cancer, with their function shaped by the tumor microenvironment.
- The new study aligns with a growing body of research showing that neutrophils can switch from tumor suppressors to tumor promoters depending on environmental cues, and that their presence often correlates with worse cancer outcomes 2 4 11 14.
- Several related studies have identified chemokines—including CCL3—as key mediators in neutrophil recruitment and function within tumors and other inflammatory diseases, supporting the mechanistic focus of the new findings 1 2 4.
- There is also evidence that targeting neutrophil recruitment or reprogramming may offer new therapeutic strategies in cancer treatment, echoing the implications of the current research 4 5 14 15.
Study Overview and Key Findings
Understanding the complex role of immune cells in cancer progression is a major challenge in oncology. This study stands out by focusing specifically on how neutrophils, typically front-line defenders against infection, are co-opted by tumors to promote disease. Through sophisticated genetic and analytical techniques, the researchers demonstrated that neutrophils exposed to the tumor milieu begin producing CCL3, a chemokine that, rather than fighting the tumor, accelerates its growth. This discovery adds a key piece to the puzzle of how the immune system can sometimes aid rather than inhibit cancer.
| Property | Value |
|---|---|
| Study Year | 2023 |
| Organization | University of Geneva, Ludwig Institute for Cancer Research |
| Journal Name | Cancer Cell |
| Authors | Mikaël Pittet, Evangelia Bolli, Pratyaksha Wirapati |
| Population | Neutrophils in various cancer types |
| Outcome | Neutrophil behavior and CCL3 production |
| Results | Neutrophils produce CCL3, promoting tumor growth across many cancers. |
Literature Review: Related Studies
To understand how these findings fit into the broader scientific context, we searched the Consensus database, which includes over 200 million research papers. The following search queries were used:
Below, key topics are summarized, highlighting how related studies inform our understanding of neutrophil function, CCL3 signaling, and immune cell roles in cancer.
| Topic | Key Findings |
|---|---|
| How do neutrophils influence tumor growth and progression? | - Neutrophils can promote tumor growth and metastasis, with high neutrophil counts linked to poor prognosis in many cancers 2 4 11 14 15. - The tumor microenvironment can reprogram neutrophils from antitumor to protumor phenotypes, affecting their impact on disease outcome 4 11 14. |
| What role does CCL3 play in immune cell recruitment and tumor biology? | - CCL3 is involved in recruiting neutrophils and other immune cells to sites of inflammation and tumors, influencing disease progression 1 2. - Leukocyte-derived CCL3 can accelerate lesion formation in atherosclerosis and is upregulated in tumor-stimulated neutrophils 1 2. |
| Are neutrophils always tumor-promoting, or can they have antitumor effects? | - Neutrophils are functionally diverse and can mediate both tumor-promoting and antitumor activities depending on context 3 6 11 12 13 14. - Certain therapies (e.g., radiotherapy, immunotherapy) can polarize neutrophils toward antitumor phenotypes 3 12 13. |
| How might targeting neutrophil activity or recruitment benefit cancer therapy? | - Reducing neutrophil recruitment or reprogramming them away from tumor-promoting states is under investigation as a therapeutic strategy 4 5 14 15. - Strategies include inhibiting chemokine receptors (CXCR1/CXCR2), altering exosome signaling, and modulating the tumor microenvironment 5 15. |
How do neutrophils influence tumor growth and progression?
The current study's finding that neutrophils can promote tumor growth by producing CCL3 echoes a substantial body of literature indicating that neutrophils, once thought to be simple defenders, play a diverse and sometimes detrimental role in cancer. Several studies have shown that high neutrophil counts or neutrophil-to-lymphocyte ratios are associated with poor outcomes, and that neutrophil behavior is shaped by the tumor microenvironment 2 4 11 14 15.
- Tumor-associated neutrophils (TANs) can facilitate angiogenesis, matrix remodeling, and metastasis 11 14.
- High infiltration of neutrophils correlates with disease aggressiveness and therapy resistance, particularly in breast cancer 2.
- The plasticity of neutrophils allows them to adapt to signals from the tumor, sometimes aiding cancer progression 11 14.
- Clinical strategies to reduce neutrophil activity are being explored as potential cancer therapies 15.
What role does CCL3 play in immune cell recruitment and tumor biology?
This study's focus on CCL3 as a key factor in neutrophil-mediated tumor progression is supported by research in both cancer and other inflammatory diseases. CCL3 is an inflammatory chemokine known to recruit neutrophils and influence their behavior in various pathological contexts 1 2.
- Leukocyte-derived CCL3 promotes neutrophil accumulation and accelerates inflammation-driven lesion development, as seen in atherosclerosis models 1.
- Tumor environments induce high CCL3 expression in neutrophils, which can further drive tumor-promoting processes 2.
- CCL3, along with other chemokines, is upregulated in cancer and may serve as a biomarker for disease progression 2.
- The regulation of CCL3 expression in immune cells is a potential therapeutic target to mitigate tumor-promoting inflammation 1 2.
Are neutrophils always tumor-promoting, or can they have antitumor effects?
The literature shows that neutrophils are not inherently tumor-promoting; their function is highly context-dependent. Some therapies can shift neutrophil activity toward tumor suppression, and certain neutrophil subsets are associated with favorable outcomes 3 6 11 12 13 14.
- Radiotherapy and immunotherapy can polarize neutrophils to antitumor phenotypes, improving treatment response 3 12 13.
- Neutrophil functional diversity is driven by cues from both the tumor and the surrounding tissue 11 14.
- Antigen-presenting neutrophils, a specific state, are linked to better survival and enhanced immune responses 13.
- Cancer immunoediting theory highlights the immune system's dual roles in suppressing and promoting cancer 6.
How might targeting neutrophil activity or recruitment benefit cancer therapy?
Consistent with the implications of the current study, several reviews and experimental studies suggest that manipulating neutrophil recruitment or function may offer new avenues for cancer therapy 4 5 14 15.
- Inhibiting neutrophil migration to tumors using chemokine receptor antagonists (e.g., CXCR1/CXCR2) is being developed as a strategy to reduce tumor-promoting inflammation 15.
- Targeting neutrophil-derived exosomes may disrupt tumor-promoting communication pathways 5.
- Preventing or reversing neutrophil reprogramming in the tumor microenvironment is a promising approach for adjuvant therapy 14.
- Understanding and altering the crosstalk between tumors and neutrophils could enable more precise and effective cancer treatments 5 14.
Future Research Questions
While this study sheds light on the role of neutrophil-derived CCL3 in cancer progression, it also highlights several unanswered questions. Further research is needed to clarify the mechanisms underlying neutrophil reprogramming, the potential for targeting CCL3 or related pathways in therapy, and the broader implications for cancer immunology and patient care.
| Research Question | Relevance |
|---|---|
| Can inhibiting CCL3 production in neutrophils improve cancer outcomes? | Targeting CCL3 may provide a new therapeutic avenue, but its effects on tumor progression and patient survival need clinical validation 1 2 4. |
| What tumor microenvironmental signals reprogram neutrophils to a pro-tumor state? | Understanding which signals drive neutrophil reprogramming could reveal new targets to prevent their tumor-promoting activity 2 4 11 14. |
| Do all cancer types utilize neutrophil CCL3 production for tumor growth? | It is unclear whether the CCL3-mediated mechanism is universal or varies by cancer type, which has implications for personalized treatment 2 11 14 15. |
| Can neutrophil reprogramming be reversed to restore antitumor activity? | Reversing neutrophil phenotype from tumor-promoting to tumor-suppressing could enhance immunotherapy efficacy 3 12 13 14. |
| How does CCL3 expression in neutrophils interact with other immune cells in the tumor microenvironment? | The broader immunological consequences of neutrophil-derived CCL3, including effects on T cells and macrophages, remain to be elucidated and could inform combination therapies 6 7 9 10 14. |