Below are 10 mechanistic studies: 
 
• 𝗔𝗹𝗹𝗲𝗿𝗴𝘆 𝗮𝗻d 𝗜𝗴𝗘 𝘀𝗶𝗴𝗻𝗮𝗹𝗶𝗻𝗴: Type I hypersensitivity is driven by allergen-specific IgE crosslinking FcεRI on mast cells, triggering rapid degranulation and systemic effects [1]. 
• 𝗖𝗔𝗥-𝗧 𝗰𝗲𝗹𝗹 𝗸𝗶𝗹𝗹𝗶𝗻𝗴: CAR-T cells bypass MHC restriction and eliminate targets via perforin–granzyme release and cytokine amplification [2]. 
• 𝗖𝘆𝘁𝗼𝗸𝗶𝗻𝗲 𝗿𝗲𝗹𝗲𝗮𝘀𝗲 𝘀𝘆𝗻𝗱𝗿𝗼𝗺𝗲 (𝗖𝗥𝗦): Excessive myeloid activation and IL-6 signaling, rather than CAR-T cells alone, as life-threatening CRS [3]. 
• 𝗥𝗲𝗴𝘂𝗹𝗮𝘁𝗼𝗿𝘆 𝗧 𝗰𝗲𝗹𝗹𝘀 (𝗧𝗿𝗲𝗴𝘀): FOXP3⁺ Tregs enforce peripheral tolerance through IL-10, TGF-β, and metabolic suppression of effector T cells [4]. 
• 𝗧𝘂𝗺𝗼𝗿 m𝗶𝗰𝗿𝗼𝗲𝗻𝘃𝗶𝗿𝗼𝗻𝗺𝗲𝗻𝘁 (𝗧𝗠𝗘): Hypoxia, nutrient deprivation, CAFs, and suppressive myeloid cells collectively blunt anti-tumor immunity [5]. 
• Oncolytic Viruses: Selective viral replication in tumor cells converts ´cold´ tumors into inflamed lesions by releasing tumor antigens and DAMPs [6]. 
• 𝗦𝘆𝗻𝘁𝗵𝗲𝘁𝗶𝗰 𝗯𝗶𝗼𝗹𝗼𝗴𝘆 𝗶𝗻 𝗶𝗺𝗺𝘂𝗻𝗶𝘁𝘆: Logic-gated receptors and modular CARs enable conditional activation, improving precision and safety [7]. 
• 𝗚𝗲𝗻𝗲 𝘁𝗵𝗲𝗿𝗮𝗽𝘆 𝘃𝗲𝗰𝘁𝗼𝗿𝘀: Lentiviral and retroviral vectors enable stable gene integration for cell therapies, while AAV favors 𝘪𝘯 𝘷𝘪𝘷𝘰 delivery with low immunogenicity [8]. 
• 𝗜𝗺𝗺𝘂𝗻𝗲 𝗰𝗵𝗲𝗰𝗸𝗽𝗼𝗶𝗻𝘁𝘀: PD-1 and CTLA-4 restrain T-cell activation at distinct stages, explaining efficacy and immune-related adverse events [9]. 
• 𝗔𝗻𝘁𝗶𝗴𝗲𝗻 𝗲𝘀𝗰𝗮𝗽𝗲 𝗮𝗻𝗱 𝗵𝗲𝘁𝗲𝗿𝗼𝗴𝗲𝗻𝗲𝗶𝘁𝘆: Tumors evolve under immune pressure, downregulating targets or MHC to evade otherwise potent therapies [10]. 
 
𝗤𝘂𝗲𝘀𝘁𝗶𝗼𝗻 𝗳𝗼𝗿 𝘁𝗵𝗲 𝗮𝘂𝗱𝗶𝗲𝗻𝗰𝗲: 
If you had to choose one mechanism to intervene on which would you target first, and why? 
 
Stay tuned for 𝗗𝗮𝘆 𝟵𝟯: 𝗙𝗲𝗲𝗱𝗲𝗿 𝗖𝗲𝗹𝗹𝘀 𝗶𝗻 𝗖𝗲𝗹𝗹 𝗖𝘂𝗹𝘁𝘂𝗿𝗲 – 𝗦𝘂𝗽𝗽𝗼𝗿𝘁𝗶𝗻𝗴 Cellular Growth 𝗠𝗮𝗶𝗻𝘁𝗲𝗻𝗮𝗻𝗰𝗲, 𝗮𝗻𝗱 𝗗𝗶𝗳𝗳𝗲𝗿𝗲𝗻𝘁𝗶𝗮𝘁𝗶𝗼𝗻 
 
𝗥𝗲𝗳𝗲𝗿𝗲𝗻𝗰𝗲𝘀 
1. DOI: 10.1038/nm.2755 
2. DOI: 10.1056/NEJMra1706169 
3. DOI: 10.1038/s41591-018-0036-4 
4. DOI: 10.3389/fimmu.2019.02486 
5. DOI: 10.1038/s41591-018-0014-x 
6. DOI: 10.1038/nbt.2287 
7. DOI: 10.1016/j.coi.2021.09.003 
8. DOI: 10.1038/s41392-021-00487-6 
9. DOI: 10.1016/j.cell.2015.03.030 
10. DOI: 10.1016/j.cell.2017.01.018 
 
#Immunology #MechanismsMatter #CancerImmunotherapy #CAR-T #SyntheticBiology #GeneTherapy #TumorMicroenvironment #Allergy #ImmuneTolerance #100DaysofImmunology