Unlike T cells, NK cells (natural killer cells) require no prior antigen sensitization. They are the innate immune system’s first-line assassins, eliminating virally infected or transformed cells within hours [1]. 

𝗠𝗲𝗰𝗵𝗮𝗻𝗶𝘀𝗺𝘀 𝗼𝗳 𝗡𝗞 𝗖𝗲𝗹𝗹 𝗞𝗶𝗹𝗹𝗶𝗻𝗴: 
1. 𝘙𝘦𝘤𝘰𝘨𝘯𝘪𝘵𝘪𝘰𝘯  Missing-self hypothesis: loss of MHC class I removes inhibition → NK activation [2]. 
2. 𝘐𝘯𝘥𝘶𝘤𝘦𝘥-𝘴𝘦𝘭𝘧: stress ligands like MICA/B activate receptors such as NKG2D. 
3. 𝘊𝘺𝘵𝘰𝘵𝘰𝘹𝘪𝘤 𝘚𝘺𝘯𝘢𝘱𝘴𝘦 𝘍𝘰𝘳𝘮𝘢𝘵𝘪𝘰𝘯  Rearrangement of cytoskeleton and polarization of lytic granules toward the target. 

𝗞𝗶𝗹𝗹𝗶𝗻𝗴 𝗣𝗮𝘁𝗵𝘄𝗮𝘆𝘀 
Perforin/granzyme pathway → pore formation and apoptosis. 
Death receptor pathway → FasL/TRAIL-mediated apoptosis. 
ADCC → FcγRIII (CD16) recognizes antibodies → antibody-dependent killing [3]. 

𝗖𝘆𝘁𝗼𝗸𝗶𝗻𝗲 𝗦𝗲𝗰𝗿𝗲𝘁𝗶𝗼𝗻 
NK cells release IFN-γ, TNF-α, boosting adaptive responses.   

𝗚𝗲𝗿𝗺𝗮𝗻 𝗖𝗼𝗻𝘁𝗿𝗶𝗯𝘂𝘁𝗶𝗼𝗻𝘀 
Carsten Watzl (Dortmund): NK receptor signaling and immune synapse [4]. 
Ulrich Kalinke (Hannover): NK cells in viral immunity [5]. 
Hermann Einsele (Würzburg): clinical translation of NK-based immunotherapies [6]. 

𝗡𝗞 𝗖𝗲𝗹𝗹𝘀 𝗶𝗻 𝗜𝗺𝗺𝘂𝗻𝗼𝘁𝗵𝗲𝗿𝗮𝗽𝘆: 𝗖𝗔𝗥-𝗡𝗞 
CAR-NK cells combine innate cytotoxicity with engineered antigen recognition. Compared to CAR-T, they carry a lower risk of cytokine release syndrome, can be developed as allogeneic “off-the-shelf” therapies, and show natural synergy with antibodies [7]. 

𝗦𝗽𝗲𝗰𝘂𝗹𝗮𝘁𝗶𝘃𝗲 𝗛𝘆𝗽𝗼𝘁𝗵𝗲𝘀𝗶𝘀 
Could dual-engineered NK cells—with CAR targeting plus metabolic reprogramming—emerge as the “universal soldiers” of immunotherapy? They might not only kill tumors directly but also reshape the tumor microenvironment to favor T and dendritic cell responses. 

Stay tuned for 𝗗𝗮𝘆 𝟭𝟱: 𝗕 𝗖𝗲𝗹𝗹𝘀 𝗮𝘁 𝗪𝗼𝗿𝗸 – 𝗧𝗵𝗲 𝗠𝗮𝗸𝗲𝗿𝘀 𝗼𝗳 𝗔𝗻𝘁𝗶𝗯𝗼𝗱𝗶𝗲𝘀 

𝗥𝗲𝗳𝗲𝗿𝗲𝗻𝗰𝗲𝘀 
1. DOI: 10.1038/ni1582 
2. DOI: 10.1016/0167-5699(90)90097-s 
3. DOI: 10.1038/nri2206 
4. DOI: 10.1016/B978-0-12-800147-9.00005-4 
5. DOI: 10.1016/j.immuni.2014.05.003 
6. DOI:10.1097/HS9.0000000000000423 
7. DOI: 10.1056/NEJMoa1910607   

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