Endogenous danger signals are molecules that are normally present in given cell compartments that are rapidly released following cell stress, damage, or non-physiologic cell death and induce immune responses. Cancer cells undergoing immunogenic cell death, which is hallmarked by the emission of various endogenous danger signals also known as damage-associated molecular patterns (DAMPs), especially alarmins, is an emerging determinant of cancer immunotherapy. Endogenous danger signals identified so far include several defensins, cathelicidins, eosinophil-associated ribonucleases, high-mobility group (HMG) proteins, heat shock proteins (HSPs), saposin-like granulysin, ion-binding proteins (e.g., S100 proteins and lactoferrin), nucleotides/metabolites (e.g., ATP and uric acid) and certain IL-1 cytokine family members (e.g., IL-1α and IL-33). These endogenous danger signals are important bridges between innate immunity and adaptive immunity and play a critical role in cancer immunology and immunotherapy.

Dendritic cells (DCs) are potent antigen-presenting cells critical in regulating adaptive immunity. Endogenous danger signals can activate immune cells, especially DCs, to stimulate immune response. Various endogenous danger signals appear to have distinct effects on the types of antigen-specific immune responses. Neutrophil-derived α-defensins have been demonstrated to induce both Th1 and Th2 immune responses upon administration together with an antigen via a mucosal route, whereas HMGN1 and β-defensins stimulate predominantly Th1 responses upon gene gun delivery to mouse epidermis as an adjuvant–antigen fusion product. In contrast, eosinophil-derived neurotoxin, a member of the eosinophil-associated ribonuclease, IL-33, and uric acid preferentially promote the development of Th2 immune responses. However, with the deepening research on endogenous danger signals, their multifaceted role in cancer immunity has gradually been revealed. For instance, earlier studies showed that HMGB1 and HSPs promote Th1 immune responses involved in protective antitumor immunity. However, follow-up studies suggested that HMGB1 only has a protective role in cancer immunity during the early stage of disease, while sustained HMGB1 recruits immunosuppressive myeloid-derived suppressor cells and regulatory T cells during cancer progression and thus also involves in maintaining immunosuppression. Therefore, the role of endogenous danger signals in cancer immunology and immunotherapy is very complex and deserves further in-depth study.

In the Research Topic “Endogenous Danger Signals in Cancer Immunology and Immunotherapy”, we would like to create an online forum for researchers to facilitate the studies on endogenous danger signals (DAMPs, including alarmins). We welcome original research articles and reviews that address the following themes:

1. Identification of additional endogenous danger signals involved in cancer immunity.

2. Mechanisms underlying the role of endogenous danger signals in cancer immunity.

3. Testing the potential use of endogenous danger signals, as adjuvants, immune stimulators, or even as therapeutic targets, for experimental cancer immunotherapy.

4. Clinical trials evaluating the efficacy of endogenous danger signal-based therapies.

Manuscripts consisting solely of bioinformatics or computational analysis of public genomic or transcriptomic databases which are not accompanied by robust and relevant validation (clinical cohort or biological validation in vitro or in vivo) are out of scope for this topic.

Submit your idea

Impact

Frontiers in Immunology

Participating Journals

Impact