Neutrophils: Rapid Respondents, Day 11

Neutrophils are the first immune cells on site in most infections and injuries. They are released in massive numbers from the bone marrow and recruited within hours.  

𝗠𝗲𝗰𝗵𝗮𝗻𝗶𝘀𝘁𝗶𝗰 𝗢𝘃𝗲𝗿𝘃𝗶𝗲𝘄 
𝘙𝘦𝘤𝘳𝘶𝘪𝘵𝘮𝘦𝘯𝘵 → Guided by chemokines such as CXCL8/IL-8 and adhesion molecules (selectins, integrins), neutrophils exit circulation and infiltrate tissues. 
𝘌𝘧𝘧𝘦𝘤𝘵𝘰𝘳 𝘧𝘶𝘯𝘤𝘵𝘪𝘰𝘯𝘴 → Phagocytosis of pathogens. 
Degranulation with proteases, myeloperoxidase, and ROS. 
𝘕𝘦𝘶𝘵𝘳𝘰𝘱𝘩𝘪𝘭 𝘦𝘹𝘵𝘳𝘢𝘤𝘦𝘭𝘭𝘶𝘭𝘢𝘳 𝘵𝘳𝘢𝘱𝘴 (𝘕𝘌𝘛𝘴) — chromatin webs coated with antimicrobial proteins. 
𝘙𝘦𝘴𝘰𝘭𝘶𝘵𝘪𝘰𝘯 → Neutrophils undergo apoptosis, then cleared by macrophages to avoid excessive tissue damage. 

This rapid choreography explains why neutrophils are sometimes called the ´emergency service´ of the immune system. 

𝗚𝗲𝗿𝗺𝗮𝗻 𝗖𝗼𝗻𝘁𝗿𝗶𝗯𝘂𝘁𝗶𝗼𝗻𝘀 
Germany has played a key role in advancing neutrophil biology: 

Arturo Zychlinsky & Volker Brinkmann (MPI Berlin) — first described NETs in 2004, a discovery that redefined neutrophils beyond phagocytosis [1]. 

Michael Hölzel & Thomas Tüting (Bonn/Magdeburg) — demonstrated that neutrophils can limit T cell–based immunotherapy via c-MET–dependent mechanisms in cancer models [2]. 

TRR-332 Collaborative Project — investigates how trained neutrophils may be harnessed for anti-tumor immunity [3]. 

Triantafyllos Chavakis (Dresden) — showed that beta-glucan training of neutrophils promotes anti-tumor phenotypes in mice, pointing to possible therapeutic applications [4]. 

𝗦𝗽𝗲𝗰𝘂𝗹𝗮𝘁𝗶𝘃𝗲 𝗛𝘆𝗽𝗼𝘁𝗵𝗲𝘀𝗶𝘀 
Could neutrophils become predictive biomarkers and therapeutic targets in immunotherapy? If baseline neutrophil states — such as their “training” status, receptor expression (e.g., c-MET), or cytokine responsiveness — were profiled, they might guide treatment selection.   

𝗘𝘃𝗲𝗻 𝗺𝗼𝗿𝗲 𝗳𝘂𝘁𝘂𝗿𝗶𝘀𝘁𝗶𝗰: neutrophils could be “trained” or engineered to serve as rapid-acting immunotherapy allies, providing an early push while T cells and adaptive responses are still mobilizing. Imagine combining CAR-T cells with trained neutrophils, creating a fast–slow tandem that enhances both immediacy and durability of anti-tumor responses.  

Stay tuned for 𝗗𝗮𝘆 𝟭𝟮: 𝗠𝗼𝗻𝗼𝗰𝘆𝘁𝗲𝘀 𝗮𝗻𝗱 𝗠𝗮𝗰𝗿𝗼𝗽𝗵𝗮𝗴𝗲𝘀 – 𝗽𝗵𝗮𝗴𝗼𝗰𝘆𝘁𝗼𝘀𝗶𝘀 

𝗥𝗲𝗳𝗲𝗿𝗲𝗻𝗰𝗲𝘀 
1. Brinkmann V, Reichard U, Goosmann C, et al. Neutrophil extracellular traps kill bacteria. Science. 2004;303(5663):1532–1535. 
2. Finisguerra V, Di Conza G, Di Matteo M, et al. MET is required for the recruitment of anti-tumoural neutrophils. Nature. 2015;522:349–353. 
3. TRR-332 Project: Dissecting the anti-tumour effects of trained neutrophils. neutrophils.de 
4. Kalafati L, Mitroulis I, Verginis P, Chavakis T. Trained immunity and neutrophils in cancer. Front Immunol. 2020;11:590147. 

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