Immunogenic cell death in cancer immunotherapy

Abstract

Cancer immunotherapy has been acknowledged as a new paradigm for cancer treatment, with notable therapeutic effects on certain cancer types. Despite their significant potential, clinical studies over the past decade have revealed that cancer immunotherapy has low response rates in the majority of solid tumors. One of the key causes for poor responses is known to be the relatively low immunogenicity of solid tumors. Because most solid tumors are immune desert 'cold tumors' with antitumor immunity blocked from the onset of innate immunity, combination therapies that combine validated T-based therapies with approaches that can increase tumor-immunogenicity are being considered as relevant therapeutic options. This review paper focuses on immunogenic cell death (ICD) as a way of enhancing immunogenicity in tumor tissues. We will thoroughly review how ICDs such as necroptosis, pyroptosis, and ferroptosis can improve anti-tumor immunity and outline clinical trials targeting ICD. Finally, we will discuss the potential of ICD inducers. as an adjuvant for cancer immunotherapy.[BMB Reports 2023; 56(5): 275-286].

Fig. 1

Role of DAMPs in ICD. (A) Induction and role of iDAMPs during ICD. (B) Induction and role of cDAMPs during ICD. (C) Activation of antitumor immunity by DAMPs.

Fig. 2

The molecular machinery of controllable ICDs. (A) The signaling pathway of necroptosis. (B) The signaling pathway of ferroptosis. (C) The signaling pathway of pyroptosis.