Avid Bioservices Inc (CDMO)

[hutschi]

Concepts and mechanisms underlying chemotherapy induced immunogenic cell death: Impact on clinical studies and considerations for combined therapies

http://www.impactjournals.com/oncotarget/index.php?journal=oncotarget&page=article&op=view&path%5B%5D=6113&path%5B%5D=15077

Extracellular and surface-exposed CALR binds to several cell surface receptors including CD69, CD91, complement component C1q and mannose binding lectin [65]. Ecto-CALR functions as a potent “eat me” signal on apoptotic cells through the binding of CD91 on macrophages and DCs [66]. Similar to CALR, phosphatidylserine (PS) also serves as an “eat me” signal on apoptotic cells, but CALR exposure precedes that of PS [22]. In contrast to CALR, PS mediates clearance of tumor cells without activating an immune response [67]. PS exposure on cancer cells has also been associated with immunosuppression, and antibody-mediated inhibition of PS significantly improves anti-tumor immune responses [68, 69]. CALR binds CD91 on APCs to promote pro-inflammatory cytokines (e.g. IL-6 and tumor necrosis factor) [70, 71]. Hence, recognition of CALR on dying cells is an early event that leads to engulfment of dying tumor cells by APCs and promotes priming of the adaptive immune response. In addition to the “eat me” signals on dying tumor cells, co-stimulatory DAMPs are required to generate an effective anti-tumor immune response (most commonly ATP and HMGB1).