Tumor cell stress-induced ligands and danger-associated molecular patterns (DAMPs)

Tumor cell stress-induced ligands and danger-associated molecular patterns (DAMPs) are a heterogeneous class of endogenous molecules that serve as critical signals for the immune system to recognize and eliminate stressed or dying malignant cells (Galluzzi et al., 2020, Nature Reviews Immunology). These molecules include surface-exposed proteins like calreticulin, secreted factors like HMGB1 and ATP, and stress-induced surface ligands such as MICA and MICB (Kroemer et al., 2022, Science). Under normal conditions, these molecules are intracellular or absent, but they are upregulated or released in response to genomic instability, metabolic stress, or cytotoxic therapy. They function by binding to specific receptors on innate immune cells—such as TLR4, P2RX7, and NKG2D—thereby facilitating the recruitment and activation of dendritic cells and natural killer cells (Raulet et al., 2013, Annual Review of Immunology). This process, often termed immunogenic cell death (ICD), is essential for the efficacy of many conventional cancer treatments, including anthracyclines and radiotherapy. However, the therapeutic challenge lies in the dual nature of these signals, as chronic DAMP signaling can sometimes promote a pro-tumorigenic inflammatory environment (Zitvogel et al., 2016, Cell).

Other names

Damage-associated molecular patternsAlarminsICD-associated moleculesStress-induced ligandsEndogenous danger signals

Induction of immunogenic cell death (ICD) and activation of pattern recognition receptors (PRRs) to stimulate anti-tumor immunity.