Critical role of immunogenic cell death in cancer therapy

Combination of Chidamide-Mediated Epigenetic Modulation with Immunotherapy: Boosting Tumor Immunogenicity and Response to PD-1/PD-L1 Blockade

“…These molecules were also considered as predominant hallmarks of ICD evaluation. Many research studies have reported that when cells were in the ICD stage, they would over-express HSP70 and/or HSP90 . As a protein with chaperone activity, an HSP could facilitate the transportation of the MHC I–peptide complex to the extracellular and/or cell surface, meanwhile enhancing the capability of DCs, such as migration and phagocytosis to apoptotic cells .…”

“…Many research studies have reported that when cells were in the ICD stage, they would over-express HSP70 and/or HSP90. 13 As a protein with chaperone activity, an HSP could facilitate the transportation of the MHC I− peptide complex to the extracellular and/or cell surface, meanwhile enhancing the capability of DCs, such as migration and phagocytosis to apoptotic cells. 46 As shown in Figure 1D, HSP70 was sharply increased even at a low treating concentration of CHI (1 μg/mL), while HSP90 exhibited moderate up-regulation in a dose-dependent manner.…”

“…11,12 These danger signals play vital roles during the activation and enhancement of antitumor immunity, such as immune cell recruitment, the capture and presentation of the tumor antigen, and so forth. 12,13 Nevertheless, only a limited number of approaches [e.g., oxaliplatin (OXA), anthracyclines, radiotherapy, photodynamic therapy (PDT), and oncolytic viruses] were verified to induce ICD response. 14 to increase tumor immunogenicity and subsequently enhance the therapeutic efficacy of ICB therapy.…”

“…Many studies have been performed to explore the effective therapeutic approaches for TNBC, including immunotherapy and immunochemotherapy. − Cancer immunotherapy, especially immune checkpoint blockade (ICB) therapy, has made revolutionary clinical advances in a variety of cancers, while the application as a single therapeutic tool can only benefit a small subset of patients, which could be attributed to a “cold” immune microenvironment. − TNBC has been considered as a “cold” tumor owing to barren tumor antigens and limited intratumoral infiltration of immune cells, which severely restricts the responsiveness and efficiency of ICB therapy. , Therefore, how to enhance antitumor immunity is the key point for TNBC immunotherapy. Growing evidence has demonstrated that the occurrence of immunogenic cell death (ICD) within a tumor can induce an effective antitumor immune response, enhancing the treatment efficiency of ICB therapy. , ICD is a type of programmed cell death, accompanied by the expression of tumor antigens and the emitting of highly immunostimulatory danger signals, such as high mobility group box 1 (HMGB1) release, calreticulin (CRT) exposure, and adenosine triphosphate (ATP) secretion. , These danger signals play vital roles during the activation and enhancement of antitumor immunity, such as immune cell recruitment, the capture and presentation of the tumor antigen, and so forth. , Nevertheless, only a limited number of approaches [ e.g. , oxaliplatin (OXA), anthracyclines, radiotherapy, photodynamic therapy (PDT), and oncolytic viruses] were verified to induce ICD response .…”

Oncolytic Viruses in Cancer Immunotherapy

“…ICD is characterized by the exposure of calreticulin (CRT) and heat shock proteins (HSP) and the release of ATP and high mobility group protein B1 (HMGB1) in the TME. [ 24 ] Endoplasmic reticulum (ER) stress and autophagy are the driving factors of exposure to CRT and ATP, respectively. The cellular lysis and disintegration allow for the release of HMGB1.…”