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. 2009 Jul 20;119(8):2127–2130. doi: 10.1172/JCI39991

Figure 2. Three mechanisms of immunochemotherapy mediated by single agents.

Figure 2

(A) An agent may simultaneously induce tumor cell apoptosis and act as a PAMP, thus activating immunostimulatory PRRs. This is the case for RIG-I and MDA-5 ligands, which, in addition to activating the innate immune system, can kill cancer cells, resulting in a combined immunochemotherapeutic effect. (B) An agent may induce tumor cell death in such a way that dying cells release danger-associated molecular patterns (DAMPs), thereby indirectly activating PRRs in innate immune effectors. For example, anthracyclines induce the exposure and release of several DAMPs on dying tumor cells (17, 18). (C) Alternatively, an anticancer agent may directly kill tumor cells and mediate an immunostimulatory off-target effect on immune cells. For example, imatinib mesylate kills tumor cells that are addicted to constitutively activated tyrosine kinases (such as Bcr/Abl in chronic myeloid leukemia and mutated c-Kit or PDGF-Ra in gastrointestinal sarcoma) at the same time that it activates innate immune effectors through an effect on c-Kit in DCs (19).