Cancer Immunotherapy: Immunogenic Cell Death
DAMPs (damage associated moleular patterns), also known as alarmins, are molecules that are released following immunogenic cell death (ICD). ICD occurs during tissue damage, infection by some oncolytic viruses, or by various chemotherapy treatments. During ICD, the release of soluble intracellular factors acts as a ‘find me’ signal that induces the infiltration of inflammatory natural killer (NK) cells, macrophages, granulocytes, and mature DC. DAMPs on the cell surface act as ‘eat me’ signals that promote phagocytosis of the damaged cell. This process does not occur in apoptosis which leads to immune tolerance. CD47 is expressed on apoptotic cells, and apoptotic bodies and interacts with SIRP alpha on phagocytes. Apoptotic bodies induce tolerance through Mer and C1q R1/CD93.
| Find Me Signals | |||
| Adenosine A2A R agonists | CX3CL1 | HSP90 | Synuclein-alpha |
| Adenosine A1 R Agonists | Genomic and mito DNA | NLRP3/NALP3 | TIM-3 |
| Adenosine A3 R Agonists | GRP78/HSPA5 | Oxidation-associated mol patterns – reactive carbonyls, peroxidized phospholipids | TLR4 agonists |
| Adenosine A2b R Agonists | Heparan sulfate | P2X R Agonists | Toll-like Receptor Agonists |
| Non-selective Adenosine R Agonists | Histones | P2Y R Agonists | Uric acid |
| CD24 | HMGB1/HMG-1 | RAGE | ZBP1/DLM-1/DAI |
| CLEC4E | HSP60 | RIG-I | |
| CLEC9a | HSP70/HSPA1A | S1P1/EDG-1 Agonists | |
| Eat Me Signals | ||
| Calreticulin | Integrin alpha V beta 5 | MFG-E8 |
| CD36/SR-B3 | JMJD6/PSR | |
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