Immunogenic Apoptotic Cell Death and Anticancer Immunity

Abstract

For many years it has been thought that apoptotic cells rapidly cleared by phagocytic cells do not trigger an immune response but rather have anti-inflammatory properties. However, accumulating experimental data indicate that certain anticancer therapies can induce an immunogenic form of apoptosis associated with the emission of damage-associated molecular patterns (DAMPs), which function as adjuvants to activate host antitumor immune responses. In this review, we will first discuss recent advances and the significance of danger signaling pathways involved in the emission of DAMPs, including calreticulin, ATP, and HMGB1. We will also emphasize that switching on a particular signaling pathway depends on the immunogenic cell death stimulus. Further, we address the role of ER stress in danger signaling and the classification of immunogenic cell death inducers in relation to how ER stress is triggered. In the final part, we discuss the role of radiotherapy-induced immunogenic apoptosis and the relationship of its immunogenicity to the fraction dose and concomitant chemotherapy.

Characterization of exosome release and extracellular vesicle-associated miRNAs for human bronchial epithelial cells irradiated with high charge and energy ions

“…Prior work implicates HSP70 and calreticulin as modulators of immune and inflammatory responses (reviewed in (Boudesco et al, 2018;De Maio, 2014;Vandenabeele et al, 2016). Notably, HSP70 has been previously identified in exosomes derived from cancer cells exposed to genotoxic stress, where it activates cytokine production via an HSP70/toll-like receptor 2/NF-κB axis (Vulpis et al, 2017).…”

DAMP—Induced Allograft and Tumor Rejection: The Circle Is Closing

“…In addition, and of note, growing clinical evidence indicates that expression of the DAMPs described here may have prognostic or predictive value for cancer patients ; a detailed description of these highly interesting data, however, is beyond the scope of this review.…”

Combination Approaches with Immune-Checkpoint Blockade in Cancer Therapy

“…ICD results in the release of tumor antigens and “danger signals,” also known as damage-associated molecular patterns (DAMPS), such as calreticulin, ATP, type I IFN, and non-histone chromatin-binding protein high-mobility group box 1 (HMGB1) (30, 31). Binding to their receptors (CD91, the purinergic receptors P2RX7 and P2RY2, IFNAR, and the toll-like receptor TLR4, respectively) on DCs, results in their activation, enhanced antigen presentation, upregulation of co-stimulatory receptors, and induction of adaptive immune responses (32), whereas cell death that is “immunologically silent” induces tolerance.…”