Figure 4.

Tumor ICD

As a result of endoplasmic reticulum (ER) stress and autophagy, dying cancer cells respond to therapeutic stress by exposing calreticulin (CRT) on their outer membrane at the pre-apoptotic stage and releasing ATP and the nuclear protein high-mobility group box 1 (HMGB1) during apoptosis. CRT, ATP, and HMGB1 bind to the receptor of immature dendritic cells (iDC), which facilitates the recruitment of iDCs into the tumor bed (stimulated by ATP), the engulfment of tumor antigens by iDCs (stimulated by CRT), and antigen presentation to T cells (stimulated by HMGB1). Activated CTLs will secret IFN-γ, which eventually leads to the inhibition of therapy-resistant tumor cells and distal tumor cells that therapeutics have not directly reached.